Submissions for variant NM_005629.4(SLC6A8):c.1428C>G (p.Tyr476Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen	RCV002465388	SCV004809058	pathogenic	Creatine transporter deficiency	2024-02-22	reviewed by expert panel	curation	The NM_005629.4: c.1428C>G (p.Tyr476Ter) variant in SLC6A8 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 10/13, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been reported a male with intellectual disability, autistic features, seizures and absent creatine peak on brain MRS (PMID: 29435807) (PP4). The variant is absent in gnomAD v2.1.1. (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 1802549). In summary, this variant meets the criteria to be classified as pathogenic for creatine transporter deficiency. SLC6A8-specific criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): PVS1, PP4, PM2_Supporting. (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on February 22, 2024).
Laboratory of Medical Genetics, University of Torino	RCV002465388	SCV002760055	likely pathogenic	Creatine transporter deficiency	2022-11-29	criteria provided, single submitter	research