Variant 3-27192225-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001394966.1(NEK10):c.2309C>T(p.Ala770Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00939 in 1,613,530 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 70 hom. )

Consequence

NEK10
NM_001394966.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.53

Variant links:

Genes affected

NEK10 (HGNC:18592): (NIMA related kinase 10) Enables protein kinase activity. Involved in several processes, including mucociliary clearance; positive regulation of protein phosphorylation; and regulation of ERK1 and ERK2 cascade. Part of protein kinase complex. Implicated in primary ciliary dyskinesia 44. [provided by Alliance of Genome Resources, Apr 2022]

NEK10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069556534).

BP6

Variant 3-27192225-G-A is Benign according to our data. Variant chr3-27192225-G-A is described in ClinVar as [Benign]. Clinvar id is 2653633.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK10	NM_001394966.1 linkuse as main transcript	c.2309C>T	p.Ala770Val	missense_variant	26/36	ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1 linkuse as main transcript	c.2309C>T	p.Ala770Val	missense_variant	26/36		NM_001394966.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00625

AC:

951

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00953

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00685

AC:

1706

AN:

248936

Hom.:

AF XY:

0.00683

AC XY:

920

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.00893

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00834

GnomAD4 exome

AF:

0.00971

AC:

14195

AN:

1461296

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

6879

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.00811

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.00793

GnomAD4 genome

AF:

0.00625

AC:

951

AN:

152234

Hom.:

Cov.:

AF XY:

0.00575

AC XY:

428

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00953

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00892

Hom.:

Bravo

AF:

0.00548

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00717

AC:

871

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

NEK10: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D;D

MetaRNN

Benign

0.0070

T;T;T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

0.95

D;D;D;D;D

PROVEAN

Benign

-1.3

N;N;.;.

REVEL

Benign

0.20

Sift

Uncertain

0.010

D;D;.;.

Sift4G

Uncertain

0.040

D;D;T;D

Polyphen

0.60

P;.;.;.

Vest4

0.71

MVP

0.77

ClinPred

0.032

GERP RS

5.6

Varity_R

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

Other links and lift over