Variant chr3-131109857-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024800.5(NEK11):c.391C>T(p.Pro131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,453,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NEK11
NM_024800.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.145

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05957353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK11	NM_024800.5 linkuse as main transcript	c.391C>T	p.Pro131Ser	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.391C>T	p.Pro131Ser	missense_variant	5/18	1	NM_024800.5	ENSP00000372857.4		Q8NG66-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000619

AC:

AN:

1453766

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

722982

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000812

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

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

Oct 17, 2023

The c.391C>T (p.P131S) alteration is located in exon 5 (coding exon 3) of the NEK11 gene. This alteration results from a C to T substitution at nucleotide position 391, causing the proline (P) at amino acid position 131 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.5

DANN

Benign

0.70

DEOGEN2

Benign

0.038

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.71

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

M_CAP

Benign

0.0019

MetaRNN

Benign

0.060

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.13

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

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.8

D;N;N;N;N;N;N

REVEL

Benign

0.027

Sift

Benign

0.15

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

Sift4G

Benign

0.38

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

Polyphen

0.047

B;B;B;B;B;B;B

Vest4

0.16

MutPred

0.43

Loss of catalytic residue at P131 (P = 0.0468);Loss of catalytic residue at P131 (P = 0.0468);Loss of catalytic residue at P131 (P = 0.0468);Loss of catalytic residue at P131 (P = 0.0468);Loss of catalytic residue at P131 (P = 0.0468);Loss of catalytic residue at P131 (P = 0.0468);Loss of catalytic residue at P131 (P = 0.0468);

MVP

0.15

MPC

0.031

ClinPred

0.062

GERP RS

-1.8

Varity_R

0.041

gMVP

0.26

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

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