Variant chr3-131109807-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024800.5(NEK11):c.341G>A(p.Arg114Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000034 in 1,587,166 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: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

NEK11
NM_024800.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

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:

NEK11 (HGNC:):

NEK11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14561197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK11	NM_024800.5 linkuse as main transcript	c.341G>A	p.Arg114Gln	missense_variant	5/18	ENST00000383366.9	NP_079076.3	Q8NG66-1B4DM56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK11	ENST00000383366.9 linkuse as main transcript	c.341G>A	p.Arg114Gln	missense_variant	5/18	1	NM_024800.5	ENSP00000372857.4		Q8NG66-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

224290

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

121332

show subpopulations

Gnomad AFR exome

AF:

0.0000669

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000607

Gnomad SAS exome

AF:

0.0000408

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000334

AC:

AN:

1435112

Hom.:

Cov.:

AF XY:

0.0000322

AC XY:

AN XY:

713302

show subpopulations

Gnomad4 AFR exome

AF:

0.0000634

Gnomad4 AMR exome

AF:

0.000935

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000517

Gnomad4 SAS exome

AF:

0.0000249

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000634

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.000115

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

Jul 20, 2021

The c.341G>A (p.R114Q) alteration is located in exon 5 (coding exon 3) of the NEK11 gene. This alteration results from a G to A substitution at nucleotide position 341, causing the arginine (R) at amino acid position 114 to be replaced by a glutamine (Q). 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

0.089

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.038

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

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D;.;.;D;D;D

M_CAP

Benign

0.0097

MetaRNN

Benign

0.15

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

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.35

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

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

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

REVEL

Benign

0.19

Sift

Benign

0.084

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

Sift4G

Benign

0.49

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

Polyphen

0.39

B;D;P;D;D;P;D

Vest4

0.42

MutPred

0.81

Gain of ubiquitination at K119 (P = 0.1047);Gain of ubiquitination at K119 (P = 0.1047);Gain of ubiquitination at K119 (P = 0.1047);Gain of ubiquitination at K119 (P = 0.1047);Gain of ubiquitination at K119 (P = 0.1047);Gain of ubiquitination at K119 (P = 0.1047);Gain of ubiquitination at K119 (P = 0.1047);

MVP

0.39

MPC

0.17

ClinPred

0.11

GERP RS

5.0

Varity_R

0.23

gMVP

0.46

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

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