ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.946C>T (p.Arg316Cys)

gnomAD frequency: 0.00006  dbSNP: rs761345213
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000638080 SCV000759560 uncertain significance Nephronophthisis 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 316 of the NPHP4 protein (p.Arg316Cys). This variant is present in population databases (rs761345213, 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: 531618). 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.
Eurofins Ntd Llc (ga) RCV000727608 SCV000854864 uncertain significance not provided 2017-12-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000764006 SCV000894958 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2022-04-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV002533211 SCV003585022 uncertain significance Inborn genetic diseases 2022-07-12 criteria provided, single submitter clinical testing The c.946C>T (p.R316C) alteration is located in exon 8 (coding exon 7) of the NPHP4 gene. This alteration results from a C to T substitution at nucleotide position 946, causing the arginine (R) at amino acid position 316 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003403467 SCV004104034 uncertain significance NPHP4-related condition 2022-08-23 criteria provided, single submitter clinical testing The NPHP4 c.946C>T variant is predicted to result in the amino acid substitution p.Arg316Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.12% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-6008176-G-A). 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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