Submissions for variant NM_000135.4(FANCA):c.3183C>T (p.Ser1061=)

gnomAD frequency: 0.00053  dbSNP: rs1800346

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000458962	SCV000558887	likely benign	Fanconi anemia	2025-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001764459	SCV001991003	uncertain significance	not provided	2019-05-29	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Genetic Services Laboratory, University of Chicago	RCV001821345	SCV002069408	likely benign	not specified	2021-04-06	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000458962	SCV002534991	uncertain significance	Fanconi anemia	2021-11-15	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001276506	SCV004017588	likely benign	Fanconi anemia complementation group A	2023-07-07	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001764459	SCV004218550	uncertain significance	not provided	2024-12-05	criteria provided, single submitter	clinical testing	The FANCA c.3183C>T (p.Ser1061=) synonymous variant has been reported in the published literature in Fanconi Anemia (PMID: 15643609 (2005)). The frequency of this variant in the general population, 0.00052 (13/24958 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on FANCA mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites. Based on the available information, we are unable to determine the clinical significance of this variant.
CeGaT Center for Human Genetics Tuebingen	RCV001764459	SCV005431963	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	FANCA: BP4, BP7
Ambry Genetics	RCV004975545	SCV005586456	likely benign	Inborn genetic diseases	2024-10-04	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.
Natera, Inc.	RCV001276506	SCV001462885	likely benign	Fanconi anemia complementation group A	2020-09-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003970325	SCV004782733	likely benign	FANCA-related disorder	2023-06-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).