ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.395C>G (p.Ala132Gly) (rs587779905)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115352 SCV000149261 uncertain significance not provided 2018-01-28 criteria provided, single submitter clinical testing This variant is denoted FANCC c.395C>G at the cDNA level, p.Ala132Gly (A132G) at the protein level, and results in the change of an Alanine to a Glycine (GCT>GGT). This variant has been observed in an individual with prostate cancer (Lu 2015). FANCC Ala132Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). FANCC Ala132Gly is located in the regions of interaction with RED, FAZF, Hsp70 and GRP94 (Gordon 2000). In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether FANCC Ala132Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000709093 SCV000481137 uncertain significance Fanconi anemia, complementation group C 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000315029 SCV000549945 uncertain significance Fanconi anemia 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 132 of the FANCC protein (p.Ala132Gly). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs587779905, ExAC 0.009%). This variant has not been reported in the literature in individuals with FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 127541). 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 glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000571052 SCV000673320 likely benign Hereditary cancer-predisposing syndrome 2018-11-28 criteria provided, single submitter clinical testing Other strong data supporting benign classification;In silico models in agreement (benign)
Mendelics RCV000709093 SCV000838358 uncertain significance Fanconi anemia, complementation group C 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000988219 SCV001137856 uncertain significance Fanconi anemia, complementation group A 2019-05-28 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.