rs140408058
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001199397.3(NEK1):c.3285C>T(p.Pro1095=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,609,494 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0030 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00039 ( 2 hom. )
Consequence
NEK1
NM_001199397.3 synonymous
NM_001199397.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.53
Genes affected
NEK1 (HGNC:7744): (NIMA related kinase 1) The protein encoded by this gene is a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. Defects in this gene are a cause of polycystic kidney disease (PKD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 4-169406685-G-A is Benign according to our data. Variant chr4-169406685-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 457136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.53 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEK1 | NM_001199397.3 | c.3285C>T | p.Pro1095= | synonymous_variant | 32/36 | ENST00000507142.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEK1 | ENST00000507142.6 | c.3285C>T | p.Pro1095= | synonymous_variant | 32/36 | 1 | NM_001199397.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00294 AC: 446AN: 151922Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00105 AC: 259AN: 246800Hom.: 2 AF XY: 0.000821 AC XY: 110AN XY: 133904
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GnomAD4 exome AF: 0.000391 AC: 570AN: 1457454Hom.: 2 Cov.: 28 AF XY: 0.000352 AC XY: 255AN XY: 725052
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GnomAD4 genome ? AF: 0.00296 AC: 450AN: 152040Hom.: 1 Cov.: 31 AF XY: 0.00279 AC XY: 207AN XY: 74294
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 30, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 28, 2017 | - - |
Short-rib thoracic dysplasia 6 with or without polydactyly Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
NEK1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at