Variant 9-124302028-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014397.6(NEK6):c.64G>T(p.Gly22Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,452,348 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: 6.9e-7 ( 0 hom. )

Consequence

NEK6
NM_014397.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

Variant links:

Genes affected

NEK6 (HGNC:7749): (NIMA related kinase 6) The protein encoded by this gene is a kinase required for progression through the metaphase portion of mitosis. Inhibition of the encoded protein can lead to apoptosis. This protein also can enhance tumorigenesis by suppressing tumor cell senescence. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

NEK6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38118455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK6	NM_014397.6 linkuse as main transcript	c.64G>T	p.Gly22Trp	missense_variant	2/10	ENST00000320246.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK6	ENST00000320246.10 linkuse as main transcript	c.64G>T	p.Gly22Trp	missense_variant	2/10	1	NM_014397.6	P1	Q9HC98-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721468

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 21, 2023

The c.166G>T (p.G56W) alteration is located in exon 3 (coding exon 2) of the NEK6 gene. This alteration results from a G to T substitution at nucleotide position 166, causing the glycine (G) at amino acid position 56 to be replaced by a tryptophan (W). 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

0.23

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

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

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.89

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

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.38

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

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

0.69

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.8

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

REVEL

Benign

0.19

Sift

Uncertain

0.0010

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

Sift4G

Pathogenic

0.0010

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

Polyphen

0.99

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

Vest4

0.57

MutPred

0.36

.;Loss of disorder (P = 0.0028);.;Loss of disorder (P = 0.0028);Loss of disorder (P = 0.0028);Loss of disorder (P = 0.0028);Loss of disorder (P = 0.0028);Loss of disorder (P = 0.0028);Loss of disorder (P = 0.0028);.;Loss of disorder (P = 0.0028);Loss of disorder (P = 0.0028);.;.;Loss of disorder (P = 0.0028);

MVP

0.66

MPC

1.1

ClinPred

0.79

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.49

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