Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: SLC6A8 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_005629.4(SLC6A8):c.1008C>T (p.Asn336=)

CA10549373

1138356 (ClinVar)

Gene: SLC6A8
Condition: creatine transporter deficiency
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 6df2223c-abbd-486c-a917-fca40a4c5e7e
Approved on: 2025-04-11
Published on: 2025-04-11

HGVS expressions

NM_005629.4:c.1008C>T
NM_005629.4(SLC6A8):c.1008C>T (p.Asn336=)
NC_000023.11:g.153693358C>T
CM000685.2:g.153693358C>T
NC_000023.10:g.152958813C>T
CM000685.1:g.152958813C>T
NC_000023.9:g.152612007C>T
NG_012016.1:g.10062C>T
NG_012016.2:g.10062C>T
ENST00000253122.10:c.1008C>T
ENST00000253122.9:c.1008C>T
ENST00000413787.1:c.154C>T
ENST00000430077.6:c.663C>T
ENST00000442457.1:c.92C>T
ENST00000467402.1:n.146-134C>T
ENST00000485324.1:n.1041C>T
NM_001142805.1:c.1008C>T
NM_001142806.1:c.663C>T
NM_005629.3:c.1008C>T
NM_001142805.2:c.1008C>T
More

Likely Benign

Met criteria codes 3
BS2 BP7 BP4
Not Met criteria codes 1
PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Cerebral Creatine Deficiency Syndromes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SLC6A8 Version 1.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_005629.4:c.1008C>T variant in SLC6A8 is a synonymous variant (p.Asn336=) with no predicted impact on splicing (all SpliceAI scores <0.1) (PMID: 37352859) (BP4, BP7). To our knowledge, this variant has not been reported in the literature and no functional studies are available. In gnomAD V4.1.0. the highest population minor allele frequency (MAF) is 0.00001456 (13/892985; 4 hemizygotes) in the European non-Finnish population. While this MAF meets the threshold for PM2_Supporting, the criterion is not met due to the presence of hemizygotes. There are 4 hemizygotes in the European non-Finnish population (BS2). There is a ClinVar entry for this variant (Variation ID: 1138356). In summary, this variant meets criteria to be classified as likely benign for creatine transporter deficiency. SLC6A8-specific ACMG/AMP criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): BS2, BP4, BP7. (Classification approved by the ClinGen CCDS VCEP on April 11, 2025)
Met criteria codes
BS2
There are 4 hemizygotes in the European non-Finnish population (BS2).
BP7
The NM_005629.4:c.1008C>T variant in SLC6A8 is a synonymous variant (p.Asn336=) with no predicted impact on splicing (all SpliceAI scores <0.1) (BP7).
BP4
The computational predictor, SpliceAI, predicts no impact on splicing (all scores <0.1) (BP4).
Not Met criteria codes
PM2
In gnomAD V4.1.0. the highest population minor allele frequency (MAF) is 0.00001456 (13/892985; 4 hemizygotes). While this MAF meets the threshold for PM2_Supporting, the criterion is not met due to the presence of hemizygotes.
Curation History
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