ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.54C>T (p.Pro18=)

gnomAD frequency: 0.00002  dbSNP: rs960874258
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen RCV002305553 SCV002600161 likely benign Deficiency of guanidinoacetate methyltransferase 2022-06-06 reviewed by expert panel curation The NM_000156.6:c.54C>T (p.Pro18=) variant in GAMT is a synonymous variant in exon 1 which is predicted to not impact splicing by SpliceAI and VarSeak, and the nucleotide is not highly conserved (BP4, BP7). The highest population minor allele frequency in a continental population of >2,000 alleles is 0.00008 in the non-Finnish European population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004). The site is covered in fewer than 50% of individuals in gnomAD v2.1.1 exomes, and therefore the allele frequency estimates may not be reliable but PM2_Supporting. This variant does not appear to have been previously reported in the published literature. However, it is noted in ClinVar (Variation ID: 696471). Although this variant may be rare, it has been classified as likely benign by the ClinGen CCDS 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).
Labcorp Genetics (formerly Invitae), Labcorp RCV000862841 SCV001003403 likely benign Cerebral creatine deficiency syndrome 2024-09-06 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003938229 SCV004753089 likely benign GAMT-related disorder 2019-04-17 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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