ClinVar Miner

Submissions for variant NM_022725.4(FANCF):c.115C>T (p.Arg39Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003276079 SCV003958646 uncertain significance Inborn genetic diseases 2023-04-27 criteria provided, single submitter clinical testing The c.115C>T (p.R39C) alteration is located in coding exon 1 of the FANCF gene. This alteration results from a C to T substitution at nucleotide position 115, causing the arginine (R) at amino acid position 39 to be replaced by a cysteine (C). Based on data from gnomAD, the T allele has an overall frequency of 0.003% (8/249962) total alleles studied. The highest observed frequency was 0.044% (8/18310) of East Asian alleles. This amino acid position is well conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003636008 SCV004520410 uncertain significance Fanconi anemia 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 39 of the FANCF protein (p.Arg39Cys). This variant is present in population databases (rs750686882, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with FANCF-related conditions. ClinVar contains an entry for this variant (Variation ID: 2534045). 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 expected to disrupt FANCF protein function with a positive predictive value of 80%. 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.

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