ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.1238T>C (p.Ile413Thr)

gnomAD frequency: 0.00006  dbSNP: rs373614448
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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) RCV000728100 SCV000855633 uncertain significance not provided 2017-07-07 criteria provided, single submitter clinical testing
Invitae RCV001366737 SCV001563051 uncertain significance Nephronophthisis 2022-04-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 413 of the NPHP4 protein (p.Ile413Thr). This variant is present in population databases (rs373614448, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. 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: 593141). 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 threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Fulgent Genetics, Fulgent Genetics RCV002485854 SCV002779622 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2022-04-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002535057 SCV003537087 uncertain significance Inborn genetic diseases 2021-10-13 criteria provided, single submitter clinical testing The c.1238T>C (p.I413T) alteration is located in exon 10 (coding exon 9) of the NPHP4 gene. This alteration results from a T to C substitution at nucleotide position 1238, causing the isoleucine (I) at amino acid position 413 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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