Submissions for variant NM_001113378.2(FANCI):c.1052A>T (p.Gln351Leu)

gnomAD frequency: 0.00020  dbSNP: rs147873714

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001118940	SCV001277262	uncertain significance	Fanconi anemia complementation group I	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.
Invitae	RCV001304617	SCV001493905	uncertain significance	Fanconi anemia	2022-04-29	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 351 of the FANCI protein (p.Gln351Leu). This variant is present in population databases (rs147873714, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. ClinVar contains an entry for this variant (Variation ID: 886652). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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	RCV002556532	SCV003756161	uncertain significance	Inborn genetic diseases	2022-09-22	criteria provided, single submitter	clinical testing	The c.1052A>T (p.Q351L) alteration is located in exon 12 (coding exon 11) of the FANCI gene. This alteration results from a A to T substitution at nucleotide position 1052, causing the glutamine (Q) at amino acid position 351 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV001118940	SCV003833927	uncertain significance	Fanconi anemia complementation group I	2019-09-10	criteria provided, single submitter	clinical testing
GeneDx	RCV003223699	SCV003919333	uncertain significance	not provided	2022-10-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge