Variant 9-124302012-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 15/21 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

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:

NEK6 (HGNC:):

NEK6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK6	NM_014397.6 linkuse as main transcript	c.48C>A	p.Asn16Lys	missense_variant	2/10	ENST00000320246.10	NP_055212.2	Q9HC98-1A0A024R8A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK6	ENST00000320246.10 linkuse as main transcript	c.48C>A	p.Asn16Lys	missense_variant	2/10	1	NM_014397.6	ENSP00000319734.5		Q9HC98-1

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

GnomAD3 exomes

AF:

0.000534

AC:

127

AN:

237686

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

128512

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 SAS 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

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.000409

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000380

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.00175

GnomAD4 genome

AF:

0.000637

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000919

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.150C>A (p.N50K) alteration is located in exon 3 (coding exon 2) of the NEK6 gene. This alteration results from a C to A substitution at nucleotide position 150, causing the asparagine (N) at amino acid position 50 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0073

.;T;.;T;T;T;T;T;.;.;T;T;.;.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.82

T;.;.;.;.;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.023

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

.;N;.;N;N;.;.;.;.;.;N;.;.;.;.

MutationTaster

Benign

0.97

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.52

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.071

Sift

Uncertain

0.021

D;T;D;T;T;T;D;T;T;D;T;T;D;D;T

Sift4G

Uncertain

0.037

D;T;T;T;T;T;D;T;T;D;T;T;D;T;T

Polyphen

0.020

B;B;B;B;B;.;.;.;.;.;B;.;B;B;.

Vest4

0.29

MutPred

0.25

.;Gain of ubiquitination at N16 (P = 0.0045);.;Gain of ubiquitination at N16 (P = 0.0045);Gain of ubiquitination at N16 (P = 0.0045);Gain of ubiquitination at N16 (P = 0.0045);Gain of ubiquitination at N16 (P = 0.0045);Gain of ubiquitination at N16 (P = 0.0045);Gain of ubiquitination at N16 (P = 0.0045);.;Gain of ubiquitination at N16 (P = 0.0045);Gain of ubiquitination at N16 (P = 0.0045);.;.;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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over