Genetic Variant NEK11:p.Glu488Val (chr3-131228591-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_024800.5(NEK11):c.1463A>T(p.Glu488Val) variant causes a missense change. The variant allele was found at a frequency of 0.674 in 1,612,750 control chromosomes in the GnomAD database, including 376,224 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.56 ( 27155 hom., cov: 32)

Exomes 𝑓: 0.69 ( 349069 hom. )

Consequence

NEK11
NM_024800.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.10

Variant links:

Genes affected

NEK11 (HGNC:18593): (NIMA related kinase 11) This gene encodes a member of the never in mitosis gene A family of kinases. The encoded protein localizes to the nucleoli, and may function with NEK2A in the S-phase checkpoint. The encoded protein appears to play roles in DNA replication and response to genotoxic stress. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2009]

NEK11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK11	NM_024800.5 link	c.1463A>T	p.Glu488Val	missense_variant	Exon 15 of 18	ENST00000383366.9	NP_079076.3	Q8NG66-1B4DM56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK11	ENST00000383366.9 link	c.1463A>T	p.Glu488Val	missense_variant	Exon 15 of 18	1	NM_024800.5	ENSP00000372857.4		Q8NG66-1

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85351

AN:

151890

Hom.:

27156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.688

Gnomad MID

AF:

0.713

Gnomad NFE

AF:

0.708

Gnomad OTH

AF:

0.584

GnomAD3 exomes

AF:

0.648

AC:

162528

AN:

250702

Hom.:

55261

AF XY:

0.663

AC XY:

89851

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.626

Gnomad ASJ exome

AF:

0.726

Gnomad EAS exome

AF:

0.387

Gnomad SAS exome

AF:

0.741

Gnomad FIN exome

AF:

0.696

Gnomad NFE exome

AF:

0.712

Gnomad OTH exome

AF:

0.677

GnomAD4 exome

AF:

0.685

AC:

1001204

AN:

1460740

Hom.:

349069

Cov.:

AF XY:

0.689

AC XY:

501019

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.630

Gnomad4 ASJ exome

AF:

0.728

Gnomad4 EAS exome

AF:

0.438

Gnomad4 SAS exome

AF:

0.743

Gnomad4 FIN exome

AF:

0.702

Gnomad4 NFE exome

AF:

0.705

Gnomad4 OTH exome

AF:

0.657

GnomAD4 genome

AF:

0.562

AC:

85358

AN:

152010

Hom.:

27155

Cov.:

AF XY:

0.563

AC XY:

41823

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.615

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.400

Gnomad4 SAS

AF:

0.727

Gnomad4 FIN

AF:

0.688

Gnomad4 NFE

AF:

0.708

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.678

Hom.:

26984

Bravo

AF:

0.538

TwinsUK

AF:

0.704

AC:

2612

ALSPAC

AF:

0.699

AC:

2695

ESP6500AA

AF:

0.260

AC:

1145

ESP6500EA

AF:

0.708

AC:

6092

ExAC

AF:

0.645

AC:

78331

Asia WGS

AF:

0.554

AC:

1928

AN:

3478

EpiCase

AF:

0.714

EpiControl

AF:

0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;.;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.58

T;T;.;T

MetaRNN

Benign

0.0000080

T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.0

.;M;M;M

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.9

D;N;N;N

REVEL

Uncertain

0.39

Sift

Benign

0.056

T;D;T;T

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.30

MPC

0.24

ClinPred

0.024

GERP RS

5.7

Varity_R

0.15

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: 3

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over