ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1643G>A (p.Arg548Gln)

gnomAD frequency: 0.00003  dbSNP: rs730881729
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160494 SCV000211059 uncertain significance not provided 2023-07-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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
Invitae RCV000630940 SCV000751915 uncertain significance Fanconi anemia 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 548 of the FANCC protein (p.Arg548Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 182492). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV001012509 SCV001172969 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-22 criteria provided, single submitter clinical testing The p.R548Q variant (also known as c.1643G>A), located in coding exon 14 of the FANCC gene, results from a G to A substitution at nucleotide position 1643. The arginine at codon 548 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genetic Services Laboratory, University of Chicago RCV001818357 SCV002069935 uncertain significance not specified 2019-11-26 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003153437 SCV003843181 uncertain significance Fanconi anemia complementation group C 2022-12-06 criteria provided, single submitter clinical testing The FANCC c.1643G>A (p.Arg548Gln) missense change has a maximum subpopulation frequency of 0.0065% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Natera, Inc. RCV000630940 SCV002081119 uncertain significance Fanconi anemia 2018-04-28 no assertion criteria provided clinical testing

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