ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1411G>A (p.Glu471Lys)

gnomAD frequency: 0.00001  dbSNP: rs543029493
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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 RCV000791646 SCV000930904 uncertain significance Fanconi anemia 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 471 of the FANCM protein (p.Glu471Lys). This variant is present in population databases (rs543029493, 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: 638962). 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 tolerated. 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.
CeGaT Center for Human Genetics Tuebingen RCV000995171 SCV001149206 uncertain significance not provided 2018-07-01 criteria provided, single submitter clinical testing
GeneDx RCV000995171 SCV001999838 uncertain significance not provided 2023-07-14 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 RCV002487632 SCV002777432 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2021-12-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV003344043 SCV004060408 uncertain significance Inborn genetic diseases 2024-11-23 criteria provided, single submitter clinical testing The p.E471K variant (also known as c.1411G>A), located in coding exon 9 of the FANCM gene, results from a G to A substitution at nucleotide position 1411. The glutamic acid at codon 471 is replaced by lysine, an amino acid with similar 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000995171 SCV005626244 uncertain significance not provided 2024-01-31 criteria provided, single submitter clinical testing The FANCM c.1411G>A (p.Glu471Lys) variant has been reported in the published literature in individuals with breast cancer as well as reportedly healthy individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). The frequency of this variant in the general population, 0.00077 (14/18150 chromosomes in East Asian subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. 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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