ClinVar Miner

Submissions for variant NM_178170.3(NEK8):c.2000C>T (p.Thr667Met)

gnomAD frequency: 0.00004  dbSNP: rs147625932
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001327457 SCV001518532 uncertain significance Nephronophthisis 9 2020-03-05 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 667 of the NEK8 protein (p.Thr667Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs147625932, ExAC 0.003%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NEK8-related conditions.
Fulgent Genetics, Fulgent Genetics RCV002504515 SCV002814145 uncertain significance Nephronophthisis 9; Renal-hepatic-pancreatic dysplasia 2 2022-01-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002546224 SCV003616198 uncertain significance Inborn genetic diseases 2022-06-24 criteria provided, single submitter clinical testing The c.2000C>T (p.T667M) alteration is located in exon 14 (coding exon 14) of the NEK8 gene. This alteration results from a C to T substitution at nucleotide position 2000, causing the threonine (T) at amino acid position 667 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.