ClinVar Miner

Submissions for variant NM_001482.3(GATM):c.1257G>A (p.Gln419=)

gnomAD frequency: 0.00001  dbSNP: rs774881489
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Total submissions: 4
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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 RCV002305513 SCV002600095 likely benign Arginine:glycine amidinotransferase deficiency 2022-06-06 reviewed by expert panel curation The NM_001482.3:c.1257G>A (p.Gln419=) variant in GATM is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not highly conserved as shown by PhyloP (BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003 (1/30612 alleles) in the South Asian population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.000055), meeting this criterion (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.0 for donor and acceptor loss suggesting that the variant has no impact on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 509542). Although this variant is rare (meeting PM2_Supporting), 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. GATM-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).
GeneDx RCV000600548 SCV000719363 likely benign not specified 2017-05-10 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Fulgent Genetics, Fulgent Genetics RCV002506463 SCV002796788 likely benign Arginine:glycine amidinotransferase deficiency; Fanconi renotubular syndrome 1 2021-10-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002305513 SCV003468513 likely benign Arginine:glycine amidinotransferase deficiency 2025-01-15 criteria provided, single submitter clinical testing

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