Genetic Variant NEK10:p.Leu513Ser (chr3-27291329-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001394966.1(NEK10):c.1538T>C(p.Leu513Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,612,430 control chromosomes in the GnomAD database, including 53,151 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4599 hom., cov: 33)

Exomes 𝑓: 0.25 ( 48552 hom. )

Consequence

NEK10
NM_001394966.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.38

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003412515).

BP6

Variant 3-27291329-A-G is Benign according to our data. Variant chr3-27291329-A-G is described in ClinVar as [Benign]. Clinvar id is 1325897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK10	NM_001394966.1 link	c.1538T>C	p.Leu513Ser	missense_variant	Exon 18 of 36	ENST00000691995.1	NP_001381895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK10	ENST00000691995.1 link	c.1538T>C	p.Leu513Ser	missense_variant	Exon 18 of 36		NM_001394966.1	ENSP00000509472.1		A0A8I5KTB8

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36037

AN:

152040

Hom.:

4598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.0942

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.271

GnomAD3 exomes

AF:

0.268

AC:

66465

AN:

247720

Hom.:

9642

AF XY:

0.272

AC XY:

36544

AN XY:

134596

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.294

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.272

GnomAD4 exome

AF:

0.252

AC:

367581

AN:

1460272

Hom.:

48552

Cov.:

AF XY:

0.254

AC XY:

184709

AN XY:

726460

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.331

Gnomad4 EAS exome

AF:

0.0908

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.237

AC:

36051

AN:

152158

Hom.:

4599

Cov.:

AF XY:

0.241

AC XY:

17931

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.0944

Gnomad4 SAS

AF:

0.286

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.263

Hom.:

14349

Bravo

AF:

0.237

TwinsUK

AF:

0.255

AC:

944

ALSPAC

AF:

0.238

AC:

919

ESP6500AA

AF:

0.168

AC:

528

ESP6500EA

AF:

0.270

AC:

1932

ExAC

AF:

0.265

AC:

31829

Asia WGS

AF:

0.185

AC:

645

AN:

3478

EpiCase

AF:

0.284

EpiControl

AF:

0.287

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24943594) -

Ciliary dyskinesia, primary, 44

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.00073

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.023

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.38

PROVEAN

Benign

0.24

.;N

REVEL

Benign

0.038

Sift

Benign

1.0

.;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0

B;.

Vest4

0.011

MPC

0.14

ClinPred

0.0018

GERP RS

2.8

Varity_R

0.037

gMVP

0.51

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