ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3329C>T (p.Ala1110Val) (rs139767853)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000081715 SCV000113646 likely benign not specified 2016-11-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,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 Clinical Services Laboratory,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)
Invitae RCV000292444 SCV000556431 benign Nephronophthisis 2020-11-27 criteria provided, single submitter clinical testing
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

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