ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.1376C>A (p.Thr459Lys)

gnomAD frequency: 0.00012  dbSNP: rs371819898
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233283 SCV000290049 uncertain significance Nephronophthisis 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 459 of the NPHP4 protein (p.Thr459Lys). This variant is present in population databases (rs371819898, gnomAD 0.1%). 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: 240964). 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 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.
Eurofins Ntd Llc (ga) RCV000728565 SCV000856157 uncertain significance not provided 2018-02-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002487080 SCV002785587 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2022-02-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002516328 SCV003687541 uncertain significance Inborn genetic diseases 2021-07-20 criteria provided, single submitter clinical testing The c.1376C>A (p.T459K) alteration is located in exon 11 (coding exon 10) of the NPHP4 gene. This alteration results from a C to A substitution at nucleotide position 1376, causing the threonine (T) at amino acid position 459 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Preventiongenetics, part of Exact Sciences RCV003401182 SCV004104770 uncertain significance NPHP4-related condition 2022-10-06 criteria provided, single submitter clinical testing The NPHP4 c.1376C>A variant is predicted to result in the amino acid substitution p.Thr459Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.082% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-5987774-G-T). Although we suspect that this variant may be benign, 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.