ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.293G>A (p.Arg98Gln)

gnomAD frequency: 0.00001  dbSNP: rs200052696
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520268 SCV000619125 uncertain significance not provided 2018-02-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the GAMT gene. The R98Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R98Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R98Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001857977 SCV002203631 uncertain significance Cerebral creatine deficiency syndrome 2022-06-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 98 of the GAMT protein (p.Arg98Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GAMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 450527). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV001834693 SCV002782141 uncertain significance Deficiency of guanidinoacetate methyltransferase 2021-12-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV001834693 SCV002087044 uncertain significance Deficiency of guanidinoacetate methyltransferase 2019-10-28 no assertion criteria provided clinical testing

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