rs370930011

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001199397.3(NEK1):c.2815A>G(p.Lys939Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

NEK1
NM_001199397.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.666

Publications

0 publications found

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]

NEK1 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis, susceptibility to, 24
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
short-rib thoracic dysplasia 6 with or without polydactyly
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
orofaciodigital syndrome type II
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Majewski type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NEK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.092820585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199397.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK1	NM_001199397.3	MANE Select	c.2815A>G	p.Lys939Glu	missense	Exon 29 of 36	NP_001186326.1
NEK1	NM_001374418.1		c.2815A>G	p.Lys939Glu	missense	Exon 28 of 35	NP_001361347.1
NEK1	NM_001374419.1		c.2731A>G	p.Lys911Glu	missense	Exon 28 of 35	NP_001361348.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK1	ENST00000507142.6	TSL:1 MANE Select	c.2815A>G	p.Lys939Glu	missense	Exon 29 of 36	ENSP00000424757.2
NEK1	ENST00000439128.6	TSL:1	c.2731A>G	p.Lys911Glu	missense	Exon 27 of 34	ENSP00000408020.2
NEK1	ENST00000511633.5	TSL:1	c.2683A>G	p.Lys895Glu	missense	Exon 28 of 35	ENSP00000423332.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000803

AC:

AN:

249084

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1461116

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726870

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39588

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111512

Other (OTH)

AF:

0.00

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not specified (1)

Short-rib thoracic dysplasia 6 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

5.0

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.051

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.59

M_CAP

Benign

0.031

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.67

PrimateAI

Benign

0.26

PROVEAN

Benign

0.0

REVEL

Benign

0.070

Sift

Benign

0.24

Sift4G

Benign

0.21

Polyphen

0.41

Vest4

0.15

MVP

0.69

MPC

0.072

ClinPred

0.13

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over