Variant 9-124313973-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014397.6(NEK6):c.282C>G(p.Ile94Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NEK6
NM_014397.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.278

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK6	NM_014397.6 linkuse as main transcript	c.282C>G	p.Ile94Met	missense_variant	4/10	ENST00000320246.10	NP_055212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK6	ENST00000320246.10 linkuse as main transcript	c.282C>G	p.Ile94Met	missense_variant	4/10	1	NM_014397.6	ENSP00000319734	P1	Q9HC98-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727200

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:

0.00000180

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

Jan 03, 2024

The c.384C>G (p.I128M) alteration is located in exon 5 (coding exon 4) of the NEK6 gene. This alteration results from a C to G substitution at nucleotide position 384, causing the isoleucine (I) at amino acid position 128 to be replaced by a methionine (M). 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

0.43

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

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

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.58

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.81

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

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.0

.;M;.;M;M;.;.;.;.;M;.;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.6

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

REVEL

Uncertain

0.45

Sift

Benign

0.061

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

Sift4G

Benign

0.076

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

Polyphen

0.99

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

Vest4

0.86

MutPred

0.70

.;Loss of ubiquitination at K98 (P = 0.1296);.;Loss of ubiquitination at K98 (P = 0.1296);Loss of ubiquitination at K98 (P = 0.1296);Loss of ubiquitination at K98 (P = 0.1296);Loss of ubiquitination at K98 (P = 0.1296);Loss of ubiquitination at K98 (P = 0.1296);.;Loss of ubiquitination at K98 (P = 0.1296);Loss of ubiquitination at K98 (P = 0.1296);.;.;Loss of ubiquitination at K98 (P = 0.1296);

MVP

0.67

MPC

2.0

ClinPred

0.99

GERP RS

-6.2

Varity_R

0.44

gMVP

0.70

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over