ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3160C>T (p.Arg1054Cys)

gnomAD frequency: 0.00007  dbSNP: rs373369949
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV000171147 SCV000221343 likely pathogenic not provided criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001058651 SCV001223237 uncertain significance Nephronophthisis 2023-07-21 criteria provided, single submitter clinical testing 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 expected to disrupt NPHP4 protein function. ClinVar contains an entry for this variant (Variation ID: 190976). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. This variant is present in population databases (rs373369949, gnomAD 0.2%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1054 of the NPHP4 protein (p.Arg1054Cys).
Fulgent Genetics, Fulgent Genetics RCV002485085 SCV002778485 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2022-05-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004535163 SCV004118460 uncertain significance NPHP4-related disorder 2022-12-07 criteria provided, single submitter clinical testing The NPHP4 c.3160C>T variant is predicted to result in the amino acid substitution p.Arg1054Cys. This variant has been reported in an individual with nephronophthisis (Abouelhoda et al 2016. PubMed ID: 27124789 Table S1) and in an individual with heterotaxy (Li S et al 2018. PubMed ID: 30120289) . This variant is reported in 0.15% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-5934602-G-A). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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