Submissions for variant NM_015102.5(NPHP4):c.3911A>G (p.His1304Arg)

gnomAD frequency: 0.00124  dbSNP: rs115488133

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176884	SCV000228642	likely benign	not specified	2016-07-26	criteria provided, single submitter	clinical testing
Invitae	RCV000864161	SCV001004925	benign	Nephronophthisis	2024-01-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001099939	SCV001256432	uncertain significance	Nephronophthisis 4	2017-09-08	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001101945	SCV001258589	uncertain significance	Senior-Loken syndrome 4	2017-09-08	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV001753581	SCV001986060	uncertain significance	not provided	2020-07-02	criteria provided, single submitter	clinical testing	Reported previously in trans with 2 other missense variants in NPHP4 in a patient with with a complex phenotype including skeletal and renal dysplasia, immunodeficiency, retinal degeneration and ovarian failure; however this proband was also noted have multiple other nonsynonomous gene variants either in the homozygous or compound heterozygous state and to have UPD2 (Carmichael et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23167750)
Mayo Clinic Laboratories, Mayo Clinic	RCV001753581	SCV004227720	uncertain significance	not provided	2022-10-05	criteria provided, single submitter	clinical testing	BS1
PreventionGenetics, part of Exact Sciences	RCV003927634	SCV004741179	likely benign	NPHP4-related condition	2019-09-17	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).