ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.5290A>G (p.Thr1764Ala)

dbSNP: rs776417170
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001913469 SCV002181592 uncertain significance Fanconi anemia 2021-04-10 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FANCM-related conditions. This variant is present in population databases (rs776417170, ExAC 0.006%). This sequence change replaces threonine with alanine at codon 1764 of the FANCM protein (p.Thr1764Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine.
GeneDx RCV003128827 SCV003805004 uncertain significance not provided 2022-08-25 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
PreventionGenetics, part of Exact Sciences RCV004738435 SCV005354827 uncertain significance FANCM-related disorder 2024-05-29 no assertion criteria provided clinical testing The FANCM c.5290A>G variant is predicted to result in the amino acid substitution p.Thr1764Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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