rs1131690774
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001199397.3(NEK1):c.1948del(p.Gln650AsnfsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000435 in 1,610,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as other (★). Synonymous variant affecting the same amino acid position (i.e. Q650Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
NEK1
NM_001199397.3 frameshift
NM_001199397.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.33
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEK1 | NM_001199397.3 | c.1948del | p.Gln650AsnfsTer2 | frameshift_variant | 23/36 | ENST00000507142.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEK1 | ENST00000507142.6 | c.1948del | p.Gln650AsnfsTer2 | frameshift_variant | 23/36 | 1 | NM_001199397.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152090Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1458294Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 725326
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ClinVar
Significance: other
Submissions summary: Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Motor neuron disease Other:1
other, criteria provided, single submitter | case-control | Centre for Genomic and Experimental Medicine, University of Edinburgh | Aug 31, 2016 | Loss-of-function but lacking segregation data Loss-of-function |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at