ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3292G>A (p.Ala1098Thr) (rs41280798)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000597836 SCV000707152 uncertain significance not provided 2018-07-06 criteria provided, single submitter clinical testing
Invitae RCV000638099 SCV000759579 uncertain significance Nephronophthisis 2020-01-07 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1098 of the NPHP4 protein (p.Ala1098Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs41280798, ExAC 0.1%). This variant has been reported in as heterozygous in several individuals affected with nephronophthisis and focal segmental glomerulosclerosis (PMID: 15776426, 26346198). However in these individuals a second, rare NPHP4 variant was not identified. ClinVar contains an entry for this variant (Variation ID: 500975). Experimental studies in a model organism, C. elegans, suggest that this missense change does not affect protein function (PMID: 21546380). 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 RCV000765245 SCV000896492 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001096629 SCV001252853 likely benign Nephronophthisis 4 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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