ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.863G>A (p.Arg288His)

gnomAD frequency: 0.00006  dbSNP: rs774872736
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001929596 SCV002198639 uncertain significance Nephronophthisis 2022-04-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 288 of the NPHP4 protein (p.Arg288His). This variant is present in population databases (rs774872736, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Fulgent Genetics, Fulgent Genetics RCV002491950 SCV002803922 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2021-11-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004538634 SCV004106371 uncertain significance NPHP4-related disorder 2023-06-21 criteria provided, single submitter clinical testing The NPHP4 c.863G>A variant is predicted to result in the amino acid substitution p.Arg288His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-6008259-C-T). 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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