Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002531425 | SCV003014700 | uncertain significance | Nephronophthisis | 2022-10-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 562354). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 860 of the NPHP4 protein (p.Gly860Glu). 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 NPHP4 protein function. 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. |
Division Of Personalized Genomic Medicine, |
RCV003453401 | SCV004190154 | uncertain significance | Senior-Loken syndrome 4 | 2020-11-05 | criteria provided, single submitter | clinical testing | The c.2579G>A variant in the NPHP4 gene is a heterozygous missense variant, which results in the substitution of the highly conserved glycine residue at the 860 position to glutamic acid (p.Gly860Glu). This variant localizes to coding exon 19 of the NPHP4 gene (30 exons total; NM_015102.5). This variant is predicted to be deleterious and damaging to protein structure and/or function based on in silico analyses (PROVEAN, SIFT, PolyPhen-2). This variant has been observed in the Genome Aggregation Database (gnomAD) at a very low frequency (allele frequency = 0.000004030, no homozygotes), indicating it is not a common benign variant in the populations represented in this database. To the best of our knowledge, this specific variant has not been described in the literature to be associated with disease. |
Gharavi Laboratory, |
RCV000681811 | SCV000809282 | likely pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research |