ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.127G>A (p.Glu43Lys)

gnomAD frequency: 0.00003  dbSNP: rs374836770
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160495 SCV000211060 uncertain significance not provided 2023-08-09 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; This variant is associated with the following publications: (PMID: Gordon2000[Book])
Mendelics RCV000988226 SCV001137863 uncertain significance Fanconi anemia complementation group A 2019-05-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV000709096 SCV001482697 uncertain significance Fanconi anemia complementation group C 2020-01-07 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Sema4, Sema4 RCV002256090 SCV002535085 uncertain significance Fanconi anemia 2022-02-02 criteria provided, single submitter curation
Ambry Genetics RCV002372044 SCV002690665 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-22 criteria provided, single submitter clinical testing The p.E43K variant (also known as c.127G>A), located in coding exon 1 of the FANCC gene, results from a G to A substitution at nucleotide position 127. The glutamic acid at codon 43 is replaced by lysine, an amino acid with 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.
Fulgent Genetics, Fulgent Genetics RCV000709096 SCV002806900 uncertain significance Fanconi anemia complementation group C 2022-01-13 criteria provided, single submitter clinical testing
Invitae RCV002256090 SCV003020355 uncertain significance Fanconi anemia 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 43 of the FANCC protein (p.Glu43Lys). This variant is present in population databases (rs374836770, gnomAD 0.02%). 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: 182493). 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 with a negative 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.
Natera, Inc. RCV000709096 SCV001463024 uncertain significance Fanconi anemia complementation group C 2018-07-02 no assertion criteria provided clinical testing

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