ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3175G>A (p.Ala1059Thr)

gnomAD frequency: 0.00024  dbSNP: rs202004152
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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) RCV000592906 SCV000709006 uncertain significance not provided 2018-06-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765247 SCV000896494 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2022-02-11 criteria provided, single submitter clinical testing
Invitae RCV001054486 SCV001218803 uncertain significance Nephronophthisis 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1059 of the NPHP4 protein (p.Ala1059Thr). This variant is present in population databases (rs202004152, gnomAD 0.1%). 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: 502319). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NPHP4 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.
Illumina Laboratory Services, Illumina RCV001098353 SCV001254713 uncertain significance Nephronophthisis 4 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV001098354 SCV001254714 uncertain significance Senior-Loken syndrome 4 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000592906 SCV001997186 uncertain significance not provided 2019-12-31 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Mayo Clinic Laboratories, Mayo Clinic RCV000592906 SCV002542174 uncertain significance not provided 2022-12-08 criteria provided, single submitter clinical testing BP4
CeGaT Center for Human Genetics Tuebingen RCV000592906 SCV004128043 likely benign not provided 2022-04-01 criteria provided, single submitter clinical testing NPHP4: BP4
GenomeConnect - Invitae Patient Insights Network RCV000765247 SCV001749809 not provided Nephronophthisis 4; Senior-Loken syndrome 4 no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 08-21-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000592906 SCV001978413 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000592906 SCV001980581 likely benign not provided no assertion criteria provided clinical testing

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