ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.2999C>G (p.Pro1000Arg)

gnomAD frequency: 0.00001  dbSNP: rs751314954
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001235155 SCV001407828 uncertain significance Fanconi anemia 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1000 of the FANCM protein (p.Pro1000Arg). This variant is present in population databases (rs751314954, gnomAD 0.06%). 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: 961461). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800973 SCV002046756 uncertain significance not provided 2024-09-23 criteria provided, single submitter clinical testing The FANCM c.2999C>G (p.Pro1000Arg) variant has not been reported in individuals with FANCM-related conditions in the published literature. The frequency of this variant in the general population, 0.00058 (20/34576 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Fulgent Genetics, Fulgent Genetics RCV002480766 SCV002786220 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2022-04-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002563823 SCV003634649 uncertain significance Inborn genetic diseases 2024-10-02 criteria provided, single submitter clinical testing The p.P1000R variant (also known as c.2999C>G), located in coding exon 14 of the FANCM gene, results from a C to G substitution at nucleotide position 2999. The proline at codon 1000 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Revvity Omics, Revvity RCV001800973 SCV003833937 uncertain significance not provided 2019-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001800973 SCV004035403 uncertain significance not provided 2023-03-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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