Submissions for variant NM_004629.2(FANCG):c.478G>A (p.Ala160Thr)

gnomAD frequency: 0.00051  dbSNP: rs140534765

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230539	SCV000288629	uncertain significance	Fanconi anemia	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 160 of the FANCG protein (p.Ala160Thr). This variant is present in population databases (rs140534765, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with FANCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 239968). 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 FANCG 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.
Illumina Laboratory Services, Illumina	RCV001166143	SCV001328483	uncertain significance	Fanconi anemia complementation group G	2018-01-13	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.
Sema4, Sema4	RCV000230539	SCV002537548	uncertain significance	Fanconi anemia	2022-03-21	criteria provided, single submitter	curation
GeneDx	RCV002307462	SCV002601108	uncertain significance	not provided	2023-12-17	criteria provided, single submitter	clinical testing	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
Fulgent Genetics, Fulgent Genetics	RCV001166143	SCV002785961	uncertain significance	Fanconi anemia complementation group G	2022-03-27	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001166143	SCV003833925	uncertain significance	Fanconi anemia complementation group G	2020-11-12	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV002307462	SCV004225022	uncertain significance	not provided	2022-07-21	criteria provided, single submitter	clinical testing	BP4_strong
Natera, Inc.	RCV001166143	SCV001452485	uncertain significance	Fanconi anemia complementation group G	2020-01-24	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003897553	SCV004717907	uncertain significance	FANCG-related disorder	2024-02-20	no assertion criteria provided	clinical testing	The FANCG c.478G>A variant is predicted to result in the amino acid substitution p.Ala160Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.20% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.