ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3011C>T (p.Thr1004Met)

gnomAD frequency: 0.00011  dbSNP: rs528511138
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000592817 SCV000705168 uncertain significance not provided 2018-08-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001058506 SCV001223083 uncertain significance Nephronophthisis 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1004 of the NPHP4 protein (p.Thr1004Met). This variant is present in population databases (rs528511138, gnomAD 0.02%). 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: 499590). 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 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.
Fulgent Genetics, Fulgent Genetics RCV002476307 SCV002800935 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2021-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV003278928 SCV004008518 uncertain significance Inborn genetic diseases 2023-05-05 criteria provided, single submitter clinical testing The c.3011C>T (p.T1004M) alteration is located in exon 21 (coding exon 20) of the NPHP4 gene. This alteration results from a C to T substitution at nucleotide position 3011, causing the threonine (T) at amino acid position 1004 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000592817 SCV001798802 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000592817 SCV001970738 uncertain significance not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004732958 SCV005346037 uncertain significance NPHP4-related disorder 2024-03-14 no assertion criteria provided clinical testing The NPHP4 c.3011C>T variant is predicted to result in the amino acid substitution p.Thr1004Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of European (Non-Finnish) 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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