ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.3232C>T (p.Pro1078Ser)

gnomAD frequency: 0.00003  dbSNP: rs189723011
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001318978 SCV001509701 uncertain significance Fanconi anemia 2024-01-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1078 of the FANCM protein (p.Pro1078Ser). This variant is present in population databases (rs189723011, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 1019537). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001760393 SCV002000602 uncertain significance not provided 2023-10-27 criteria provided, single submitter clinical testing 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 RCV001760393 SCV004218762 uncertain significance not provided 2023-04-13 criteria provided, single submitter clinical testing To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00024 (6/24648 chromosomes, http://gnomad.broadinstitute.org), is uninformative in 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.
Ambry Genetics RCV004034951 SCV004868401 likely benign Inborn genetic diseases 2024-02-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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