Submissions for variant NM_000507.4(FBP1):c.490G>A (p.Gly164Ser)

gnomAD frequency: 0.00001  dbSNP: rs121918188

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center	RCV000000916	SCV000537874	pathogenic	Fructose-biphosphatase deficiency	2017-03-27	criteria provided, single submitter	clinical testing
Invitae	RCV000000916	SCV000818890	pathogenic	Fructose-biphosphatase deficiency	2023-10-27	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 164 of the FBP1 protein (p.Gly164Ser). This variant is present in population databases (rs121918188, gnomAD 0.01%). This missense change has been observed in individual(s) with fructose-1,6-bisphosphatase deficiency (PMID: 9382095, 20096900, 25601412, 27101822). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 868). 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 expected to disrupt FBP1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects FBP1 function (PMID: 9382095, 20096900). For these reasons, this variant has been classified as Pathogenic.
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV000000916	SCV004035247	likely pathogenic	Fructose-biphosphatase deficiency	2022-12-21	criteria provided, single submitter	clinical testing
OMIM	RCV000000916	SCV000021066	pathogenic	Fructose-biphosphatase deficiency	1997-10-01	no assertion criteria provided	literature only