ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.157T>A (p.Trp53Arg) (rs1131691837)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492861 SCV000582973 likely pathogenic not provided 2016-04-14 criteria provided, single submitter clinical testing The W53R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The W53R 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R48C, R51L/Q, G55C) have been reported in the Human Gene Mutation Database in association with galactosemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000634555 SCV000755877 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2018-01-09 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 53 of the GALT protein (p.Trp53Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GALT-related disease. ClinVar contains an entry for this variant (Variation ID: 430221). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; 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.

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