ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.2203C>T (p.Arg735Trp)

gnomAD frequency: 0.00096  dbSNP: rs191913664
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724060 SCV000226650 uncertain significance not provided 2018-05-10 criteria provided, single submitter clinical testing
GeneDx RCV000724060 SCV000513951 uncertain significance not provided 2022-11-05 criteria provided, single submitter clinical testing Identified in individuals with nephronophthisis in published literature, although a second NPHP4 variant was not reported for one individual and the other individual had variants in a different gene that may have also contributed to the phenotype (Hoefele et al., 2005; Davis et al., 2011); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 15776426, 21258341, 34426522, 32865313, 32483926)
Labcorp Genetics (formerly Invitae), Labcorp RCV001088494 SCV001000798 likely benign Nephronophthisis 2025-01-23 criteria provided, single submitter clinical testing
Mendelics RCV000986226 SCV001135158 uncertain significance Nephronophthisis 4 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001100471 SCV001256993 uncertain significance Senior-Loken syndrome 4 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV000986226 SCV001259092 uncertain significance Nephronophthisis 4 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Mayo Clinic Laboratories, Mayo Clinic RCV000724060 SCV002542285 uncertain significance not provided 2022-01-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005025279 SCV005661017 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2023-12-30 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV000724060 SCV001923361 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000724060 SCV001969051 uncertain significance not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004537377 SCV004116667 uncertain significance NPHP4-related disorder 2024-05-01 no assertion criteria provided clinical testing The NPHP4 c.2203C>T variant is predicted to result in the amino acid substitution p.Arg735Trp. This variant along with two other NPHP4 variants (c.2951C>T, p.Thr984Met and c.2965G>A, p.Glu989Lys) were reported in an individual with Senior–Løken syndrome (Sallum et al. 2020. PubMed ID: 32865313). This variant was also found in the heterozygous state or along with the c.2965G>A, p.Glu989Lys in individuals with nephronophthisis (Hoefele et al. 2005. PubMed ID: 15776426; Tables S2 and S3, König et al. 2022. PubMed ID: 36090483). This variant was also documented in an individual from a retinal dystrophy cohort (Table S12, Diñeiro et al. 2020. PubMed ID: 32483926). This variant is reported in 0.21% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may possibly be benign, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.

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