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

gnomAD frequency: 0.00011  dbSNP: rs528511138

Total submissions: 6

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
Invitae	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