The NM_000156.6 : c.419C>A (p.Ser140Ter) variant in GAMT is a nonsense variant that is predicted to cause a premature stop codon in biologically-relevant exon 4/6 that leads to nonsense mediated decay in a gene in which loss-of-function is an established mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in the lietarture in individuals with GAMT deficiency. There is a ClinVar entry for this variant (Variation ID: 225369). The classification of this variant has been upgraded from Variant of Uncertain Significance to Likely Pathogenic based on the recommendations of the ClinGen Sequence Variant Interpretation Working Group, that a variant meeting PVS1 and PM2_Supporting is classified as Likely Pathogenic (https://clinicalgenome.org/site/assets/files/5182/pm2_-_svi_recommendation_-_approved_sept2020.pdf ). GAMT-specific ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0): PVS1, PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).