ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.5066C>T (p.Ala1689Val)

gnomAD frequency: 0.00002  dbSNP: rs759068569
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001907574 SCV002123684 uncertain significance Fanconi anemia 2023-10-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1689 of the FANCM protein (p.Ala1689Val). This variant is present in population databases (rs759068569, gnomAD 0.003%). 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: 1361430). 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 valine 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.
Fulgent Genetics, Fulgent Genetics RCV002503414 SCV002792988 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2022-03-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002548026 SCV003619987 likely benign Inborn genetic diseases 2022-05-04 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478885 SCV004218813 uncertain significance not provided 2022-11-16 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000011 (3/282524 chromosomes,, is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with breast cancer as well as in unaffected controls (PMID: 33471991 (2021), see also LOVD ( 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.

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