Submissions for variant NM_015102.5(NPHP4):c.3329C>T (p.Ala1110Val)

gnomAD frequency: 0.00374  dbSNP: rs139767853

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081715	SCV000113646	likely benign	not specified	2016-11-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001093742	SCV000358428	likely benign	Nephronophthisis 4	2018-01-13	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000331197	SCV000358429	likely benign	Senior-Loken syndrome 4	2018-01-13	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001573175	SCV000513952	likely benign	not provided	2018-03-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22550138, 26260382)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000292444	SCV000556431	benign	Nephronophthisis	2024-01-31	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000081715	SCV002071208	likely benign	not specified	2019-07-17	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294019	SCV002587744	uncertain significance	Kidney disorder	2017-05-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498430	SCV002808941	likely benign	Nephronophthisis 4; Senior-Loken syndrome 4	2022-04-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001573175	SCV004128041	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	NPHP4: BP4, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV001573175	SCV005258127	likely benign	not provided		criteria provided, single submitter	not provided
Sydney Genome Diagnostics, Children's Hospital Westmead	RCV000292444	SCV001449373	uncertain significance	Nephronophthisis	2019-07-23	no assertion criteria provided	clinical testing	This individual is also heterozygous for the c.3329C>T variant in the NPHP4 gene, which results in the amino acid substitution of alanine to valine at residue 1110, p.(Ala1110Val). To our knowledge, this variant has not been previously reported in the literature or any disease specific databases to be a disease causing variant. The variant is listed in ClinVar multiple times as both a benign variant and a VOUS. This variant has been reported in the gnomAD browser (http://gnomad.broadinstitute.org) with a low allele frequency of 0.36% (998 out of 276,100 alleles including 3 homozygous individuals). In silico analysis of pathogenicity (through Alamut Visual v2.8.1) using PolyPhen2, SIFT and MutationTaster all suggest that this variant is likely to be benign. This variant is considered to be a VOUS according to the ACMG guidelines (Evidence used: BP4).
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573175	SCV001798628	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001573175	SCV001917546	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001573175	SCV001927063	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573175	SCV001964744	likely benign	not provided		no assertion criteria provided	clinical testing