ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1424C>T (p.Thr475Met) (rs761957732)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476812 SCV000547746 uncertain significance Fanconi anemia 2019-12-05 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 475 of the FANCA protein (p.Thr475Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs761957732, ExAC 0.002%) but has not been reported in the literature in individuals with a FANCA-related disease. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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