ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.35A>G (p.Tyr12Cys)

dbSNP: rs762884109
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482075 SCV000567483 uncertain significance not provided 2015-07-30 criteria provided, single submitter clinical testing This variant is denoted FANCC c.35A>G at the cDNA level, p.Tyr12Cys (Y12C) at the protein level, and results in the change of a Tyrosine to a Cysteine (TAT>TGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Tyr12Cys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Tyrosine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. FANCC Tyr12Cys occurs at a position that is not conserved and is located in the RED binding domain (Gordon 2000). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether FANCC Tyr12Cys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV002350058 SCV002619477 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-14 criteria provided, single submitter clinical testing The p.Y12C variant (also known as c.35A>G), located in coding exon 1 of the FANCC gene, results from an A to G substitution at nucleotide position 35. The tyrosine at codon 12 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002525805 SCV003517222 uncertain significance Fanconi anemia 2022-08-03 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 12 of the FANCC protein (p.Tyr12Cys). This variant is present in population databases (rs762884109, gnomAD 0.006%). 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: 419583). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Natera, Inc. RCV001276467 SCV001462838 uncertain significance Fanconi anemia complementation group C 2020-09-16 no assertion criteria provided clinical testing

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