ClinVar Miner

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

gnomAD frequency: 0.00004  dbSNP: rs761957732
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000476812 SCV000547746 uncertain significance Fanconi anemia 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 475 of the FANCA protein (p.Thr475Met). This variant is present in population databases (rs761957732, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 408174). 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: "Possibly 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.
Fulgent Genetics, Fulgent Genetics RCV002489042 SCV002787997 uncertain significance Fanconi anemia complementation group A 2022-02-24 criteria provided, single submitter clinical testing
GeneDx RCV003317216 SCV004021454 uncertain significance not provided 2023-01-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003317216 SCV005625420 uncertain significance not provided 2024-10-02 criteria provided, single submitter clinical testing The FANCA c.1424C>T (p.Thr475Met) variant has been reported in the published literature in in an individual with cutaneous melanoma (PMID: 29641532 (2018)). This variant has also been identified as a somatic variant in a prostate cancer tumor sample (PMID: 31874108 (2020)). The frequency of this variant in the general population, 0.000023 (3/129160 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000476812 SCV002095034 uncertain significance Fanconi anemia 2020-10-08 no assertion criteria provided clinical testing

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