Submissions for variant NM_153240.5(NPHP3):c.3756C>G (p.Ser1252Arg)

gnomAD frequency: 0.00065  dbSNP: rs143451766

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176699	SCV000228396	uncertain significance	not provided	2018-09-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000814429	SCV000954839	likely benign	Nephronophthisis	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001147808	SCV001308654	uncertain significance	Renal-hepatic-pancreatic dysplasia 1	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001147809	SCV001308655	uncertain significance	NPHP3-related Meckel-like syndrome	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001147810	SCV001308656	uncertain significance	Nephronophthisis 3	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Center for Human Genetics Tuebingen	RCV000176699	SCV001501878	uncertain significance	not provided	2020-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000176699	SCV001824778	likely benign	not provided	2020-11-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 12872122, 21228398)
Clinical Genetics, Academic Medical Center	RCV000176699	SCV001919178	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000176699	SCV001964048	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004537410	SCV004115053	uncertain significance	NPHP3-related disorder	2024-02-07	no assertion criteria provided	clinical testing	The NPHP3 c.3756C>G variant is predicted to result in the amino acid substitution p.Ser1252Arg. This variant was reported in one family with nephronophthisis 3 and a second variant in NPHP3 was not identified (Family F50, Olbrich et al 2003. PubMed ID: 12872122). This variant is reported in 0.12% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including one homozygous individual, which may be too frequent to be a disease causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.