Submissions for variant NM_080632.3(UPF3B):c.1372A>G (p.Ser458Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003410624	SCV004116282	uncertain significance	UPF3B-related disorder	2022-09-26	criteria provided, single submitter	clinical testing	The UPF3B c.1372A>G variant is predicted to result in the amino acid substitution p.Ser458Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-118968921-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003512223	SCV004370002	uncertain significance	Syndromic X-linked intellectual disability 14	2023-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 458 of the UPF3B protein (p.Ser458Gly). 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. 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 UPF3B protein function. This variant has not been reported in the literature in individuals affected with UPF3B-related conditions. This variant is present in population databases (rs367726987, gnomAD 0.02%).