Submissions for variant NM_000507.4(FBP1):c.730C>T (p.Arg244Trp)

gnomAD frequency: 0.00028  dbSNP: rs200679026

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000197614	SCV000251408	uncertain significance	not provided	2021-09-10	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; This variant is associated with the following publications: (PMID: 30167848, 31589614)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000991167	SCV001064332	benign	Fructose-biphosphatase deficiency	2024-01-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000991167	SCV001327774	uncertain significance	Fructose-biphosphatase deficiency	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.
Reproductive Health Research and Development, BGI Genomics	RCV000991167	SCV001142397	uncertain significance	Fructose-biphosphatase deficiency	2020-01-06	no assertion criteria provided	curation	NM_000507.3:c.730C>T in the FBP1 gene has an allele frequency of 0.01 in Ashkenazi Jewish subpopulation in the gnomAD database including one homozygous occurrence. Pathogenic computational verdict because pathogenic predictions from DANN, DEOGEN2, EIGEN, FATHMM-MKL, M-CAP, MVP, MutationAssessor, MutationTaster, PrimateAI, REVEL and SIFT. Taken together, we interprete this variant as variant of uncertain significance (VUS). ACMG/AMP criteria applied: BS1, PP3.
PreventionGenetics, part of Exact Sciences	RCV003967518	SCV004783345	likely benign	FBP1-related disorder	2021-05-28	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).