ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.2035A>G (p.Thr679Ala)

gnomAD frequency: 0.00016  dbSNP: rs201642456
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000597180 SCV000708372 uncertain significance not provided 2018-06-13 criteria provided, single submitter clinical testing
Invitae RCV001343111 SCV001537073 uncertain significance Nephronophthisis 2022-09-30 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 679 of the NPHP4 protein (p.Thr679Ala). This variant is present in population databases (rs201642456, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 501860). 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. 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.
PreventionGenetics, part of Exact Sciences RCV003420044 SCV004117286 uncertain significance NPHP4-related condition 2023-08-29 criteria provided, single submitter clinical testing The NPHP4 c.2035A>G variant is predicted to result in the amino acid substitution p.Thr679Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.070% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-5964785-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.