ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3131G>A (p.Arg1044His) (rs375819124)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727684 SCV000855016 uncertain significance not provided 2018-01-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001100141 SCV001256647 uncertain significance Nephronophthisis 4 2017-04-28 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 Clinical Services Laboratory,Illumina RCV001100142 SCV001256648 uncertain significance Senior-Loken syndrome 4 2017-04-28 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.
Invitae RCV001243786 SCV001416968 uncertain significance Nephronophthisis 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1044 of the NPHP4 protein (p.Arg1044His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs375819124, ExAC 0.07%). This variant has not been reported in the literature in individuals 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, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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