ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.2809C>T (p.Leu937Phe)

gnomAD frequency: 0.00017  dbSNP: rs138274490
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000823317 SCV000964171 uncertain significance Fanconi anemia 2023-12-28 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 937 of the FANCM protein (p.Leu937Phe). This variant is present in population databases (rs138274490, gnomAD 0.08%). 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: 665106). 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 phenylalanine 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.
Baylor Genetics RCV001293944 SCV001482646 uncertain significance Spermatogenic failure 28 2020-01-22 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001772139 SCV002001238 uncertain significance not provided 2023-05-08 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
Fulgent Genetics, Fulgent Genetics RCV002478929 SCV002784984 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2022-02-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002535981 SCV003691764 likely benign Inborn genetic diseases 2022-09-07 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.
PreventionGenetics, part of Exact Sciences RCV004538129 SCV004115306 uncertain significance FANCM-related disorder 2023-04-20 criteria provided, single submitter clinical testing The FANCM c.2809C>T variant is predicted to result in the amino acid substitution p.Leu937Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.077% of alleles in individuals of African descent in gnomAD (, which is more common than expected for a primary cause of disease. Although we suspect that this variant may be benign, 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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