Genetic Variant NEK6:p.Val160Leu (chr9-124326402-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014397.6(NEK6):c.478G>T(p.Val160Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V160M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NEK6
NM_014397.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.81

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22935742).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014397.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEK6	NM_014397.6	MANE Select	c.478G>T	p.Val160Leu	missense	Exon 6 of 10	NP_055212.2
NEK6	NM_001145001.3		c.580G>T	p.Val194Leu	missense	Exon 7 of 11	NP_001138473.1	Q9HC98-2
NEK6	NM_001166171.2		c.580G>T	p.Val194Leu	missense	Exon 7 of 11	NP_001159643.1	Q9HC98-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEK6	ENST00000320246.10	TSL:1 MANE Select	c.478G>T	p.Val160Leu	missense	Exon 6 of 10	ENSP00000319734.5	Q9HC98-1
NEK6	ENST00000373600.7	TSL:1	c.580G>T	p.Val194Leu	missense	Exon 7 of 11	ENSP00000362702.3	Q9HC98-2
NEK6	ENST00000540326.5	TSL:1	c.532G>T	p.Val178Leu	missense	Exon 6 of 10	ENSP00000441469.1	Q9HC98-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458460

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725656

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111936

Other (OTH)

AF:

0.00

AC:

AN:

60364

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.021

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0062

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

PhyloP100

4.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

1.3

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0060

Vest4

0.47

MutPred

0.68

Loss of catalytic residue at V160 (P = 0.0626)

MVP

0.45

MPC

1.0

ClinPred

0.73

GERP RS

5.1

Varity_R

0.096

gMVP

0.59

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over