Submissions for variant NM_000136.3(FANCC):c.1156T>C (p.Ser386Pro)

gnomAD frequency: 0.00236  dbSNP: rs41281202

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000120969	SCV000211068	benign	not specified	2014-08-15	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001082314	SCV000253074	benign	Fanconi anemia	2024-01-31	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224016	SCV000281484	uncertain significance	not provided	2015-06-04	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Ambry Genetics	RCV000566496	SCV000673296	likely benign	Hereditary cancer-predisposing syndrome	2019-03-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics	RCV000988205	SCV001137842	likely benign	Fanconi anemia complementation group A	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000120969	SCV001363458	likely benign	not specified	2019-02-01	criteria provided, single submitter	clinical testing	Variant summary: FANCC c.1156T>C (p.Ser386Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00074 in 277128 control chromosomes, predominantly at a frequency of 0.0079 within the African subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 4.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in FANCC causing Fanconi Anemia Group C phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1156T>C in individuals affected with Fanconi Anemia Group C and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign (3x) and once as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Baylor Genetics	RCV000709083	SCV001525765	uncertain significance	Fanconi anemia complementation group C	2018-07-16	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000224016	SCV002046913	benign	not provided	2021-04-29	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000120969	SCV002066055	likely benign	not specified	2021-08-27	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001082314	SCV002535082	likely benign	Fanconi anemia	2021-02-25	criteria provided, single submitter	curation
ITMI	RCV000120969	SCV000085137	not provided	not specified	2013-09-19	no assertion provided	reference population