ClinVar Miner

Submissions for variant NM_001482.3(GATM):c.314C>T (p.Pro105Leu)

dbSNP: rs147804855
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Total submissions: 2
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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 RCV003159110 SCV003852695 uncertain significance Arginine:glycine amidinotransferase deficiency 2023-01-24 reviewed by expert panel curation The NM_001482.3:c.314C>T variant in GATM is a missense variant that is predicted to result in the substitution of proline by leucine and amino acid position 105 (p.Pro105Leu). To our knowledge, this variant has not been reported in an individual with AGAT deficiency in the published literature. It is absent in gnomAD v2.1.1. (PM2_Supporting). When overexpressed in HeLa cells, the variant resulted in <15% of wild-type activity (PMID: 27233232) (PS3_Supporting). The computational predictor REVEL gives a score of 0.066 which is below the threshold of 0.15, evidence that does not predict a damaging effect on AGAT function (BP4). There is a ClinVar entry for this variant (Variation ID: 225913). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for AGAT deficiency. GATM-specific ACMG/AMP criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): PS3_Supporting, PM2_Supporting, BP4. (Classification approved by the ClinGen CCDS VCEP on January 25, 2023).
Hospital for Sick Children RCV000488911 SCV000267661 not provided not provided no assertion provided in vitro

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