Genetic Variant NEK6:p.Asn16Lys (chr9-124302012-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014397.6(NEK6):c.48C>A(p.Asn16Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,606,512 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.00064 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

NEK6
NM_014397.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

Publications

4 publications found

Variant links:

Genes affected

NEK6 (HGNC:7749): (NIMA related kinase 6) The protein encoded by this gene is a kinase required for progression through the metaphase portion of mitosis. Inhibition of the encoded protein can lead to apoptosis. This protein also can enhance tumorigenesis by suppressing tumor cell senescence. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

NEK6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02319485).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014397.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEK6	NM_014397.6	MANE Select	c.48C>A	p.Asn16Lys	missense	Exon 2 of 10	NP_055212.2
NEK6	NM_001145001.3		c.150C>A	p.Asn50Lys	missense	Exon 3 of 11	NP_001138473.1	Q9HC98-2
NEK6	NM_001166171.2		c.150C>A	p.Asn50Lys	missense	Exon 3 of 11	NP_001159643.1	Q9HC98-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEK6	ENST00000320246.10	TSL:1 MANE Select	c.48C>A	p.Asn16Lys	missense	Exon 2 of 10	ENSP00000319734.5	Q9HC98-1
NEK6	ENST00000373600.7	TSL:1	c.150C>A	p.Asn50Lys	missense	Exon 3 of 11	ENSP00000362702.3	Q9HC98-2
NEK6	ENST00000540326.5	TSL:1	c.102C>A	p.Asn34Lys	missense	Exon 2 of 10	ENSP00000441469.1	Q9HC98-3

Frequencies

GnomAD3 genomes

AF:

0.000637

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00115

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000534

AC:

127

AN:

237686

AF XY:

0.000467

show subpopulations

Gnomad AFR exome

AF:

0.000272

Gnomad AMR exome

AF:

0.000418

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000482

Gnomad NFE exome

AF:

0.000993

Gnomad OTH exome

AF:

0.000343

GnomAD4 exome

AF:

0.00101

AC:

1470

AN:

1454218

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

727

AN XY:

722622

show subpopulations

African (AFR)

AF:

0.000420

AC:

AN:

33324

American (AMR)

AF:

0.000409

AC:

AN:

43986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25912

East Asian (EAS)

AF:

0.00

AC:

AN:

39414

South Asian (SAS)

AF:

0.00

AC:

AN:

84538

European-Finnish (FIN)

AF:

0.0000380

AC:

AN:

52680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00120

AC:

1331

AN:

1108544

Other (OTH)

AF:

0.00175

AC:

105

AN:

60062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.000637

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41552

American (AMR)

AF:

0.000196

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00115

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000956

Hom.:

Bravo

AF:

0.000661

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000519

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.82

M_CAP

Benign

0.014

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

PhyloP100

1.5

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.52

REVEL

Benign

0.071

Sift

Uncertain

0.021

Sift4G

Uncertain

0.037

Polyphen

0.020

Vest4

0.29

MutPred

0.25

Gain of ubiquitination at N16 (P = 0.0045)

MVP

0.48

MPC

0.39

ClinPred

0.016

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.20

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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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

Computational scores

Splicing

Publications

Other links and lift over