rs10510592

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L513A) has been classified as Uncertain significance.

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

Publications

27 publications found

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 Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 44
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NEK10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394966.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK10	NM_001394966.1	MANE Select	c.1538T>C	p.Leu513Ser	missense	Exon 18 of 36	NP_001381895.1
NEK10	NM_001394970.1		c.1538T>C	p.Leu513Ser	missense	Exon 18 of 38	NP_001381899.1
NEK10	NM_152534.6		c.1538T>C	p.Leu513Ser	missense	Exon 19 of 39	NP_689747.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK10	ENST00000691995.1	MANE Select	c.1538T>C	p.Leu513Ser	missense	Exon 18 of 36	ENSP00000509472.1
NEK10	ENST00000429845.6	TSL:5	c.1538T>C	p.Leu513Ser	missense	Exon 19 of 39	ENSP00000395849.2
NEK10	ENST00000341435.9	TSL:2	c.1538T>C	p.Leu513Ser	missense	Exon 19 of 25	ENSP00000343847.5

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

GnomAD2 exomes

AF:

0.268

AC:

66465

AN:

247720

AF XY:

0.272

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 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

African (AFR)

AF:

0.152

AC:

5087

AN:

33462

American (AMR)

AF:

0.378

AC:

16849

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

8650

AN:

26106

East Asian (EAS)

AF:

0.0908

AC:

3604

AN:

39674

South Asian (SAS)

AF:

0.294

AC:

25289

AN:

86088

European-Finnish (FIN)

AF:

0.270

AC:

14406

AN:

53376

Middle Eastern (MID)

AF:

0.395

AC:

2275

AN:

5762

European-Non Finnish (NFE)

AF:

0.249

AC:

276186

AN:

1110902

Other (OTH)

AF:

0.253

AC:

15235

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

13368

26736

40103

53471

66839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9252

18504

27756

37008

46260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.237

AC:

36051

AN:

152158

Hom.:

4599

Cov.:

AF XY:

0.241

AC XY:

17931

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.153

AC:

6371

AN:

41518

American (AMR)

AF:

0.342

AC:

5225

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1157

AN:

3470

East Asian (EAS)

AF:

0.0944

AC:

490

AN:

5188

South Asian (SAS)

AF:

0.286

AC:

1376

AN:

4814

European-Finnish (FIN)

AF:

0.272

AC:

2882

AN:

10580

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17555

AN:

67990

Other (OTH)

AF:

0.268

AC:

567

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1389

2779

4168

5558

6947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.258

Hom.:

20031

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Ciliary dyskinesia, primary, 44 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.00073

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.023

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

PhyloP100

2.4

PrimateAI

Benign

0.38

PROVEAN

Benign

0.24

REVEL

Benign

0.038

Sift

Benign

1.0

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.011

MPC

0.14

ClinPred

0.0018

GERP RS

2.8

PromoterAI

0.0090

Neutral

(source)

Varity_R

0.037

gMVP

0.51

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over