ClinVar Miner

Submissions for variant NM_001199397.3(NEK1):c.1063A>G (p.Arg355Gly)

gnomAD frequency: 0.00003  dbSNP: rs35763578
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796428 SCV000935941 uncertain significance Short-rib thoracic dysplasia 6 with or without polydactyly 2023-07-25 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with NEK1-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NEK1 protein function. ClinVar contains an entry for this variant (Variation ID: 642879). This variant is present in population databases (rs35763578, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 355 of the NEK1 protein (p.Arg355Gly).
Illumina Laboratory Services, Illumina RCV000796428 SCV001306882 likely benign Short-rib thoracic dysplasia 6 with or without polydactyly 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003117586 SCV003799567 uncertain significance not provided 2022-03-15 criteria provided, single submitter clinical testing The NEK1 c.1063A>G; p.Arg355Gly variant (rs35763578), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 642879). This variant is found in the general population with an overall allele frequency of 0.0066% (13/196588 alleles) in the Genome Aggregation Database. The arginine at codon 355 is moderately conserved, and computational analyses predict that this variant is neutral (REVEL: 0.082). Due to limited information, the clinical significance of this variant is uncertain at this time.
GeneDx RCV003117586 SCV003923940 uncertain significance not provided 2022-11-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27527004)

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