The NM_000156.6:c.328G>T variant in GAMT is a missense variant predicted to cause substitution of valine by phenylalanine at amino acid 110 (p.Val110Phe). The variant was found in compound heterozygosity, phase unknown, with a pathogenic variant in GAMT (c.327G>A) in one patient with elevated guanidinoacetate in urine and a partially absent creatine peak on brain magentic resonance spectroscopy (PMID 24415674) (PP4_Strong, PM3_Supporting). Expression of the variant in fibroblasts resulted in no detectable fusion protein when the variant was expressed in GAMT-deficient fibroblasts indicating that this variant may impact protein function (PMID 24415674)(PS3_Supporting). The computational predictor REVEL gives a score of 0.928 which is above the threshold of 0.75, evidence that correlates with impact to GAMT function (PP3). This variant is absent in gnomAD v.2.1.1 (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 205580. In summary, this variant meets the criteria to be classified as Likely pathogenic for GAMT deficiency. GAMT-specific ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0): PP4_strong, PS3_Supporting, PM3_Supporting, PM2_Supporting, PP3. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).