ClinVar

Description

The NM_000156.6:c.39C>A (p.Gly13=) variant in GAMT is a synonymous variant in exon 1. It is absent in gnomAD v2.1.1 (PM2_Supporting); however, this region has low coverage and, therefore, the allele frequency data may not be accurate. It is predicted to not impact splicing by SpliceAI and VarSeak, and the nucleotide is not highly conserved (BP4, BP7). This variant does not appear to have been reported in the published literature. It is noted in ClinVar (Variation ID: 544263). Although this variant may be rare, it has been classified as likely benign by the ClinGen Creatine Deficiency Syndromes (CCDS) Variant Curation Expert Panel (VCEP) based on the recommendation of Richards et al (PMID: 25741868) because it is a synonymous variant, the altered nucleotide is not highly conserved, computational prediction suggests no impact on splicing, and there is no additional evidence to suggest that the variant is disease-causing. GAMT-specific ACMG/AMP criteria applied, as specified by the CCDS VCEP (Specifications Version 1.1.0): PM2_Supporting, BP4, BP7. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).