ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.367A>G (p.Thr123Ala)

gnomAD frequency: 0.00001  dbSNP: rs771827261
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725990 SCV000341053 uncertain significance not provided 2016-05-14 criteria provided, single submitter clinical testing
GeneDx RCV000337338 SCV000492314 uncertain significance not specified 2016-12-01 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the GAMT gene. The T123A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T123A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T123A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other 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. 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 RCV000706359 SCV000835403 uncertain significance Cerebral creatine deficiency syndrome 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 123 of the GAMT protein (p.Thr123Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs771827261, ExAC 0.003%). 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: 287314). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV004021220 SCV004873733 uncertain significance Inborn genetic diseases 2024-02-12 criteria provided, single submitter clinical testing The c.367A>G (p.T123A) alteration is located in exon 3 (coding exon 3) of the GAMT gene. This alteration results from a A to G substitution at nucleotide position 367, causing the threonine (T) at amino acid position 123 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001833373 SCV002087035 uncertain significance Deficiency of guanidinoacetate methyltransferase 2020-12-30 no assertion criteria provided clinical testing

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