Variant 14-75087227-G-T 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_033116.6(NEK9):c.2608C>A(p.Pro870Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,604,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NEK9
NM_033116.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.669

Variant links:

Genes affected

NEK9 (HGNC:18591): (NIMA related kinase 9) This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein is activated in mitosis and, in turn, activates other family members during mitosis. This protein also mediates cellular processes that are essential for interphase progression. [provided by RefSeq, Jul 2016]

NEK9 links:

ZC2HC1C (HGNC:20354): (zinc finger C2HC-type containing 1C) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZC2HC1C links:

Genome browser will be placed here

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=0.09414807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK9	NM_033116.6 linkuse as main transcript	c.2608C>A	p.Pro870Thr	missense_variant	21/22	ENST00000238616.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK9	ENST00000238616.10 linkuse as main transcript	c.2608C>A	p.Pro870Thr	missense_variant	21/22	1	NM_033116.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250302

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1452172

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720184

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:

0.00000634

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.2608C>A (p.P870T) alteration is located in exon 21 (coding exon 21) of the NEK9 gene. This alteration results from a C to A substitution at nucleotide position 2608, causing the proline (P) at amino acid position 870 to be replaced by a threonine (T). 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

0.061

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.092

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.64

M_CAP

Benign

0.076

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.77

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.87

REVEL

Benign

0.076

Sift

Benign

0.22

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.12

MutPred

0.18

Gain of relative solvent accessibility (P = 0.0166);

MVP

0.72

MPC

0.43

ClinPred

0.096

GERP RS

5.3

Varity_R

0.044

gMVP

0.17

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