NM_001199397.3:c.418G>T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001199397.3(NEK1):​c.418G>T​(p.Gly140*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,352,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

NEK1
NM_001199397.3 stop_gained

Scores

5
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.78
Variant links:
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 rank MANE Protein UniProt
NEK1NM_001199397.3 linkc.418G>T p.Gly140* stop_gained Exon 7 of 36 ENST00000507142.6 NP_001186326.1 Q96PY6-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEK1ENST00000507142.6 linkc.418G>T p.Gly140* stop_gained Exon 7 of 36 1 NM_001199397.3 ENSP00000424757.2 Q96PY6-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.39e-7
AC:
1
AN:
1352580
Hom.:
0
Cov.:
25
AF XY:
0.00000150
AC XY:
1
AN XY:
668686
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000135
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.66
CADD
Pathogenic
39
DANN
Uncertain
0.99
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.99
D
Vest4
0.94
GERP RS
5.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-170510644; API