chr4-169507095-TG-T
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001199397.3(NEK1):βc.1948delβ(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 (β ). 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: π 0.0000066 ( 0 hom., cov: 31)
Exomes π: 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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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152090Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74320
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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 |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at