dbSNP rs11543198: CLK3:c.153-22G>A (chr15-74619987-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001130028.2(CLK3):c.153-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 1,613,622 control chromosomes in the GnomAD database, including 6,902 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.071 ( 907 hom., cov: 33)

Exomes 𝑓: 0.056 ( 5995 hom. )

Consequence

CLK3
NM_001130028.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.526

Publications

19 publications found

Variant links:

Genes affected

CLK3 (HGNC:2071): (CDC like kinase 3) This gene encodes a protein belonging to the serine/threonine type protein kinase family. This protein is a nuclear dual-specificity kinase that regulates the intranuclear distribution of the serine/arginine-rich (SR) family of splicing factors. Two transcript variants encoding different isoforms have been found for this gene. Related pseudogenes are located on chromosomes 1 and 9. [provided by RefSeq, Jul 2008]

CLK3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029336512).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLK3	NM_001130028.2 link	c.153-22G>A		intron_variant	Intron 2 of 12	ENST00000395066.9	NP_001123500.2
CLK3	NM_003992.5 link	c.153-22G>A		intron_variant	Intron 2 of 12		NP_003983.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLK3	ENST00000395066.9 link	c.153-22G>A		intron_variant	Intron 2 of 12	1	NM_001130028.2	ENSP00000378505.4

Frequencies

GnomAD3 genomes

AF:

0.0708

AC:

10765

AN:

152118

Hom.:

901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0592

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0347

Gnomad OTH

AF:

0.0839

GnomAD2 exomes

AF:

0.110

AC:

27600

AN:

250566

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.0405

Gnomad AMR exome

AF:

0.380

Gnomad ASJ exome

AF:

0.0331

Gnomad EAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.0558

Gnomad NFE exome

AF:

0.0327

Gnomad OTH exome

AF:

0.0902

GnomAD4 exome

AF:

0.0561

AC:

81932

AN:

1461386

Hom.:

5995

Cov.:

AF XY:

0.0567

AC XY:

41246

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.0395

AC:

1321

AN:

33474

American (AMR)

AF:

0.368

AC:

16450

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0341

AC:

890

AN:

26130

East Asian (EAS)

AF:

0.227

AC:

9001

AN:

39692

South Asian (SAS)

AF:

0.115

AC:

9937

AN:

86254

European-Finnish (FIN)

AF:

0.0494

AC:

2627

AN:

53186

Middle Eastern (MID)

AF:

0.0532

AC:

307

AN:

5766

European-Non Finnish (NFE)

AF:

0.0338

AC:

37540

AN:

1111802

Other (OTH)

AF:

0.0639

AC:

3859

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

4250

8499

12749

16998

21248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1748

3496

5244

6992

8740

<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:

0.0708

AC:

10784

AN:

152236

Hom.:

907

Cov.:

AF XY:

0.0766

AC XY:

5700

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0415

AC:

1726

AN:

41550

American (AMR)

AF:

0.257

AC:

3924

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3470

East Asian (EAS)

AF:

0.237

AC:

1224

AN:

5164

South Asian (SAS)

AF:

0.117

AC:

566

AN:

4830

European-Finnish (FIN)

AF:

0.0592

AC:

628

AN:

10602

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0347

AC:

2362

AN:

68024

Other (OTH)

AF:

0.0830

AC:

175

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

481

962

1443

1924

2405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0525

Hom.:

1514

Bravo

AF:

0.0854

TwinsUK

AF:

0.0321

AC:

119

ALSPAC

AF:

0.0340

AC:

131

ESP6500AA

AF:

0.0380

AC:

167

ESP6500EA

AF:

0.0345

AC:

296

ExAC

AF:

0.0960

AC:

11654

Asia WGS

AF:

0.165

AC:

570

AN:

3478

EpiCase

AF:

0.0343

EpiControl

AF:

0.0343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0071

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0029

PhyloP100

-0.53

PROVEAN

Benign

-0.41

Sift

Uncertain

0.015

Sift4G

Benign

0.081

GERP RS

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over