ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.490C>T (p.His164Tyr)

gnomAD frequency: 0.00003  dbSNP: rs761063669
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594673 SCV000704462 uncertain significance not provided 2016-12-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001373466 SCV001570183 uncertain significance Nephronophthisis 2022-03-18 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 164 of the NPHP4 protein (p.His164Tyr). This variant is present in population databases (rs761063669, gnomAD 0.03%). This missense change has been observed in individual(s) with congenital heart defects and situs inversus (PMID: 22550138). ClinVar contains an entry for this variant (Variation ID: 499123). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV000594673 SCV001986061 uncertain significance not provided 2019-07-02 criteria provided, single submitter clinical testing Identified in a patient with cardiac laterality defects in published literature, however, this individual's presumably unaffected father also harbored this variant (French et al., 2012); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22550138)
PreventionGenetics, part of Exact Sciences RCV004732956 SCV005358756 uncertain significance NPHP4-related disorder 2024-06-12 no assertion criteria provided clinical testing The NPHP4 c.490C>T variant is predicted to result in the amino acid substitution p.His164Tyr. This variant has been reported as heterozygous in an individual with cardiovascular malformations (French et al 2012. PubMed ID: 22550138). The variant was inherited from the father of unknown phenotype. This variant is reported in 0.032% of alleles in individuals of Latino descent in gnomAD. 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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