{
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    "assertionMethod": {
      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243096",
      "label": "ClinGen Cerebral Creatine Deficiency Syndromes Expert Panel Specifications to the ACMG/AMP\nVariant Interpretation Guidelines for GAMT Version 1",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "1.0.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0012999",
      "id": "MONDO:0012999",
      "label": "guanidinoacetate methyltransferase deficiency",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/el/0/1594",
        "evidenceItem": [
          {
            "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/ei/1/1595",
            "contribution": [
              {
                "agent": {
                  "@id": "https://genboree.org/evrepo/api//agent/CG_50047_EP167964246022374",
                  "id": "CG-PCER-AGENT:CG_50047_EP167964246022374",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2022/10/7",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0017",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000220",
                "id": "SEPIO:0000220",
                "label": "Pathogenic Very Strong"
              },
              "id": "0017",
              "label": "PVS1",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/el/0/1594/1596",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402996122/MONDO:0012999/026/ci/CA402996122/MONDO:0012999/026.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://genboree.org/evrepo/api//agent/CG_50047_EP167964246022374",
                          "id": "CG-PCER-AGENT:CG_50047_EP167964246022374",
                          "type": "Agent"
                        },
                        "comments": "The NM_000156.6:c.316C>T (p.Gln106Ter) variant in GAMT is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 2/6 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).",
                        "contributionDate": {
                          "date": "2022/10/7",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
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                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA402996122/MONDO:0012999/026/ci/CA402996122/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/0/1594",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://genboree.org/evrepo/api//agent/CG_50047_EP167964246022374",
                  "id": "CG-PCER-AGENT:CG_50047_EP167964246022374",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2022/10/7",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0030",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000329",
                "id": "SEPIO:0000329",
                "label": "Pathogenic Supporting"
              },
              "id": "0030",
              "label": "PM2",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402996122/MONDO:0012999/026/ci/CA402996122/MONDO:0012999/026.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://genboree.org/evrepo/api//agent/CG_50047_EP167964246022374",
                          "id": "CG-PCER-AGENT:CG_50047_EP167964246022374",
                          "type": "Agent"
                        },
                        "comments": "This variant is absent in gnomAD v2.1.1 (PM2_Supporting).",
                        "contributionDate": {
                          "date": "2022/10/7",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA402996122/MONDO:0012999/026/ci/CA402996122/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/el/0/1738",
        "evidenceItem": [
          {
            "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/ei/1/1739",
            "contribution": [
              {
                "agent": {
                  "@id": "https://genboree.org/evrepo/api//agent/CG_50047_EP167964246022374",
                  "id": "CG-PCER-AGENT:CG_50047_EP167964246022374",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2022/10/7",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/005",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000330",
                "id": "SEPIO:0000330",
                "label": "Pathogenic Strong"
              },
              "id": "005",
              "label": "PP4",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/el/0/1738/1740",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402996122/MONDO:0012999/026/ci/CA402996122/MONDO:0012999/026.002",
                    "contribution": [
                      {
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                          "@id": "https://genboree.org/evrepo/api//agent/CG_50047_EP167964246022374",
                          "id": "CG-PCER-AGENT:CG_50047_EP167964246022374",
                          "type": "Agent"
                        },
                        "comments": "At least 2 patients with this variant have been reported with clinical features consistent with GAMT deficiency, elevated guanidinoacetate in urine or plasma, and low or absent creatine peak on brain magnetic resonance spectroscopy (MRS) (PMID:  20049533, 24415674, 29506905); one of these patients also had evidence of a guanidinoacetate peak on brain MRS (PP4_Strong).",
                        "contributionDate": {
                          "date": "2022/10/7",
                          "description": "Date on which this evidence was provided"
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                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA402996122/MONDO:0012999/026/ci/CA402996122/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/0/1738/1740",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/0/1738",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/ei/1/1718",
            "contribution": [
              {
                "agent": {
                  "@id": "https://genboree.org/evrepo/api//agent/CG_50047_EP167964246022374",
                  "id": "CG-PCER-AGENT:CG_50047_EP167964246022374",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2022/10/7",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/007",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "007",
              "label": "PM3",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://genboree.org/evrepo/api/interpretation/CA402996122/MONDO:0012999/026/el/0/1717/1719",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA402996122/MONDO:0012999/026/ci/CA402996122/MONDO:0012999/026.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://genboree.org/evrepo/api//agent/CG_50047_EP167964246022374",
                          "id": "CG-PCER-AGENT:CG_50047_EP167964246022374",
                          "type": "Agent"
                        },
                        "comments": "Two patients with this variant (with different descriptions) are compound heterozygous for the variant and c.407C>T (p.Thr136Met); phase unknown (PMID 20049533, 29506905). The in trans data from this patient will be used in the assessment of p.Thr136Met and is not included here to avoid circular logic. Therefore, PM3 is not met at the current time.",
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                          "date": "2022/10/7",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA402996122/MONDO:0012999/026/ci/CA402996122/MONDO:0012999/026.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/0/1717/1719",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026/0/1717",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA402996122/MONDO:0012999/026",
    "metadata": {
      "created": "2024-09-23T20:09:41.136Z",
      "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.",
      "producedAtUTC": "Mon, 23 Sep 2024 20:09:41 -0000",
      "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)",
      "version": "1.0.0"
    },
    "statementOutcome": {
      "@id": "https://loinc.org/LA6668-3",
      "id": "LN:LA6668-3",
      "label": "Pathogenic"
    },
    "type": "VariantPathogenicityInterpretation",
    "uuid": "3452b82d-9e59-452b-9384-d0d089d383be",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA402996122",
      "id": "CAR:CA402996122",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000156.6:c.316C>T"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000156.6(GAMT):c.316C>T (p.Gln106Ter)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://genboree.org/evrepo/api/summarysrvc",
      "when": "2026-06-12T03:13:36.965Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}