ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.821C>T (p.Pro274Leu)

gnomAD frequency: 0.00001  dbSNP: rs752624938
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000728265 SCV000855818 uncertain significance not provided 2017-07-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477681 SCV002787183 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2022-04-30 criteria provided, single submitter clinical testing
Invitae RCV002535063 SCV003025240 uncertain significance Nephronophthisis 2022-08-22 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 274 of the NPHP4 protein (p.Pro274Leu). ClinVar contains an entry for this variant (Variation ID: 593270). 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. 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 leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.

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