{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/3fee475c-7628-4c86-a0c7-ffcd348b9fe7/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1562840326", "label": "ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for FOXN1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0011132", "id": "MONDO:0011132", "label": "T-cell immunodeficiency, congenital alopecia, and nail dystrophy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1717", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/ei/1/1718", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "contributionDate": { "date": "2024/7/29", "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/CA915949637/MONDO:0011132/113/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "comments": "Pt1 is compound heterozygous with c.1089_1103del which has not yet been classified by the SCID VCEP (PMID: 31566583).", "contributionDate": { "date": "2024/7/29", "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": "CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1717", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1594", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/ei/1/1595", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "contributionDate": { "date": "2024/7/29", "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/CA915949637/MONDO:0011132/113/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "comments": "This frameshift variant in exon 7, of 9, results in a premature stop codon in exon 8, which is predicted to cause NMD (PVS1).", "contributionDate": { "date": "2024/7/29", "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": "CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1594", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1633", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/ei/1/1634", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "contributionDate": { "date": "2024/7/29", "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/0063", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0063", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "comments": "The variant was detected by exome sequencing with Sanger confirmation in one patient (Pt 1) with normal hair and nails but T-B+NK+ SCID. They had Undetectable TRECs, at 3 months CD3 31 cells/uL (2500-5500) (0.5pt), CD8 3 (500-1700), NK 188 (170-1100), CD19+ 2159 (300-2000), (PMID: 31566583; PP4).", "contributionDate": { "date": "2024/7/29", "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": "CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1633", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1636", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/ei/1/1637", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "contributionDate": { "date": "2024/7/29", "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/CA915949637/MONDO:0011132/113/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "comments": "This variant is absent from gnomADv4.0 (PM2_supporting).", "contributionDate": { "date": "2024/7/29", "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": "CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1636", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1828", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/ei/1/1829", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "contributionDate": { "date": "2024/7/29", "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/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "comments": "Expression vectors containing Foxn1 variants were transfected into HeLa cells along with the β5t-luciferase reporter construct, a well-defined transcriptional target of Foxn1. This variant resulted in 0.90% activity in the reporter assay compared to WT (PMID: 37419334).\n\nThis evidence is not considered here since this variant was used as a Pathogenic control for this assay.", "contributionDate": { "date": "2024/7/29", "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": "CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1828", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1735", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/ei/1/1736", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "contributionDate": { "date": "2024/7/29", "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/0053", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0053", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA915949637/MONDO:0011132/113/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50091_EP170474609917003", "id": "CG-PCER-AGENT:CG_50091_EP170474609917003", "type": "Agent" }, "comments": "One heterozygous case has been reported (SCV001579576.3) with a consistent phenotype 0.25pt (PS4_NotMet).", "contributionDate": { "date": "2024/7/29", "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": "CA915949637/MONDO:0011132/113/ci/CA915949637/MONDO:0011132/113.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA915949637/MONDO:0011132/113", "metadata": { "created": "2024-09-23T22:40:25.834Z", "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 22:40:25 -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": "3fee475c-7628-4c86-a0c7-ffcd348b9fe7", "variant": { "@id": "https://reg.genome.network/allele/CA915949637", "id": "CAR:CA915949637", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001369369.1:c.933_936dup" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001369369.1(FOXN1):c.933_936dup (p.Asp313fs)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-05-08T15:52:24.753Z" } }, "status": { "code": 200, "name": "OK" } }