Submissions for variant NM_014669.5(NUP93):c.1772G>T (p.Gly591Val)

gnomAD frequency: 0.00014  dbSNP: rs145473779

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Biology Laboratory, Fundació Puigvert	RCV000210563	SCV001425128	likely pathogenic	Nephrotic syndrome, type 12	2020-02-01	criteria provided, single submitter	research
GeneDx	RCV001799635	SCV002043967	likely pathogenic	not provided	2021-12-10	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect; this variant fails to interact and reduces translocation of SMAD4 (Braun et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function and splicing; This variant is associated with the following publications: (PMID: 31517150, 30577294, 26878725, 33578576, 29869118, 33532864)
Invitae	RCV001799635	SCV002233611	pathogenic	not provided	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 591 of the NUP93 protein (p.Gly591Val). This variant is present in population databases (rs145473779, gnomAD 0.03%). This missense change has been observed in individual(s) with steroid-resistant nephrotic syndrome (PMID: 26878725). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 224964). 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 NUP93 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NUP93 function (PMID: 26878725). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000210563	SCV000266815	pathogenic	Nephrotic syndrome, type 12	2020-11-20	no assertion criteria provided	literature only
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare	RCV000210563	SCV000863893	pathogenic	Nephrotic syndrome, type 12	2018-05-30	no assertion criteria provided	clinical testing
Yale Center for Mendelian Genomics, Yale University	RCV001849346	SCV002107013	likely pathogenic	Nephrotic syndrome	2017-11-10	no assertion criteria provided	literature only