ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1464G>C (p.Arg488Ser)

gnomAD frequency: 0.00001  dbSNP: rs1415434775
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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 RCV000692215 SCV000820027 uncertain significance Fanconi anemia 2023-08-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 488 of the FANCC protein (p.Arg488Ser). This variant is not present in population databases (gnomAD 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: 571161). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCC 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002060874 SCV002495753 uncertain significance Fanconi anemia complementation group C 2021-11-24 criteria provided, single submitter clinical testing FANCC NM_000136.2 exon 14 p.Arg488Ser (c.1464G>C): This variant has not been reported in the literature but is present in 0.001% (1/68030) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-95107135-C-G?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:571161). This variant amino acid Serine (Ser) is present in 1 reptilian species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV002388236 SCV002698791 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-23 criteria provided, single submitter clinical testing The p.R488S variant (also known as c.1464G>C), located in coding exon 13 of the FANCC gene, results from a G to C substitution at nucleotide position 1464. The arginine at codon 488 is replaced by serine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002060874 SCV002784944 uncertain significance Fanconi anemia complementation group C 2021-11-12 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002060874 SCV003843089 uncertain significance Fanconi anemia complementation group C 2023-08-17 criteria provided, single submitter clinical testing The FANCC c.1464G>C (p.Arg488Ser) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but this prediction has not been confirmed by functional studies. 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.?
GeneDx RCV003322809 SCV004028101 uncertain significance not provided 2023-08-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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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