Variant chr3-131133858-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.549G>A(p.Met183Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,611,564 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 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

NEK11
NM_024800.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.59

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=0.12611261).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK11	NM_024800.5 linkuse as main transcript	c.549G>A	p.Met183Ile	missense_variant	7/18	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.549G>A	p.Met183Ile	missense_variant	7/18	1	NM_024800.5	ENSP00000372857.4		Q8NG66-1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000400

AC:

AN:

250220

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135298

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000336

AC:

AN:

1459402

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726050

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.000263

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00

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:

0.0000487

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

Nov 08, 2022

The c.549G>A (p.M183I) alteration is located in exon 7 (coding exon 5) of the NEK11 gene. This alteration results from a G to A substitution at nucleotide position 549, causing the methionine (M) at amino acid position 183 to be replaced by an isoleucine (I). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

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

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

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

M_CAP

Benign

0.019

MetaRNN

Benign

0.13

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

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.18

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

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.6

D;D;D;D;D;D;D

REVEL

Benign

0.12

Sift

Benign

0.060

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

Sift4G

Benign

0.14

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

Polyphen

0.40

B;P;B;P;P;B;P

Vest4

0.47

MutPred

0.47

Gain of catalytic residue at L188 (P = 0.047);Gain of catalytic residue at L188 (P = 0.047);Gain of catalytic residue at L188 (P = 0.047);Gain of catalytic residue at L188 (P = 0.047);Gain of catalytic residue at L188 (P = 0.047);Gain of catalytic residue at L188 (P = 0.047);Gain of catalytic residue at L188 (P = 0.047);

MVP

0.44

MPC

0.12

ClinPred

0.18

GERP RS

5.5

Varity_R

0.53

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

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