Submissions for variant NM_080916.3(DGUOK):c.758A>G (p.Asn253Ser)

gnomAD frequency: 0.00006  dbSNP: rs200169027

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000726205	SCV000251328	likely benign	not provided	2011-10-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000726205	SCV000342881	uncertain significance	not provided	2016-06-08	criteria provided, single submitter	clinical testing
Invitae	RCV000726205	SCV002180182	uncertain significance	not provided	2022-09-10	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 253 of the DGUOK protein (p.Asn253Ser). This variant is present in population databases (rs200169027, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with DGUOK-related conditions. ClinVar contains an entry for this variant (Variation ID: 214289). 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 DGUOK protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000726205	SCV002541844	uncertain significance	not provided	2023-01-12	criteria provided, single submitter	clinical testing	BP4, PM2
Ambry Genetics	RCV003298259	SCV003995329	uncertain significance	Inborn genetic diseases	2023-04-28	criteria provided, single submitter	clinical testing	The c.758A>G (p.N253S) alteration is located in exon 6 (coding exon 6) of the DGUOK gene. This alteration results from a A to G substitution at nucleotide position 758, causing the asparagine (N) at amino acid position 253 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.