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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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	P49761-1B3KRI8
CLK3	NM_003992.5 link	c.153-22G>A		intron_variant	Intron 2 of 12		NP_003983.2	P49761-1

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		P49761-1

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

GnomAD3 exomes

AF:

0.110

AC:

27600

AN:

250566

Hom.:

3658

AF XY:

0.102

AC XY:

13817

AN XY:

135440

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 SAS exome

AF:

0.118

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

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.0341

Gnomad4 EAS exome

AF:

0.227

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.0494

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0639

GnomAD4 genome

AF:

0.0708

AC:

10784

AN:

152236

Hom.:

907

Cov.:

AF XY:

0.0766

AC XY:

5700

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0415

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.0320

Gnomad4 EAS

AF:

0.237

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.0592

Gnomad4 NFE

AF:

0.0347

Gnomad4 OTH

AF:

0.0830

Alfa

AF:

0.0488

Hom.:

595

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

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0071

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0029

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over