Genetic Variant NEK11:p.Glu55Gln (chr3-131029871-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024800.5(NEK11):c.163G>C(p.Glu55Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NEK11
NM_024800.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33924457).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK11	NM_024800.5	MANE Select	c.163G>C	p.Glu55Gln	missense	Exon 3 of 18	NP_079076.3
NEK11	NM_001321221.2		c.163G>C	p.Glu55Gln	missense	Exon 3 of 19	NP_001308150.1
NEK11	NM_001353022.2		c.163G>C	p.Glu55Gln	missense	Exon 3 of 19	NP_001339951.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEK11	ENST00000383366.9	TSL:1 MANE Select	c.163G>C	p.Glu55Gln	missense	Exon 3 of 18	ENSP00000372857.4	Q8NG66-1
NEK11	ENST00000510688.5	TSL:1	c.163G>C	p.Glu55Gln	missense	Exon 2 of 16	ENSP00000423458.1	Q8NG66-4
NEK11	ENST00000507910.5	TSL:1	c.163G>C	p.Glu55Gln	missense	Exon 2 of 14	ENSP00000426662.1	Q8NG66-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251358

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111980

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0083

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.13

PhyloP100

3.9

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.3

REVEL

Benign

0.18

Sift

Benign

0.20

Sift4G

Benign

0.15

Polyphen

0.95

Vest4

0.32

MutPred

0.75

Gain of MoRF binding (P = 0.0259)

MVP

0.48

MPC

0.22

ClinPred

0.43

GERP RS

5.7

PromoterAI

0.024

Neutral

(source)

Varity_R

0.26

gMVP

0.43

Mutation Taster

=78/22

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over