dbSNP rs56298217: CLK3:c.466+92G>A (chr15-74622308-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001130028.2(CLK3):c.466+92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,279,338 control chromosomes in the GnomAD database, including 3,294 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 0.046 ( 291 hom., cov: 33)

Exomes 𝑓: 0.056 ( 3003 hom. )

Consequence

CLK3
NM_001130028.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

Publications

7 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLK3	NM_001130028.2 link	c.466+92G>A		intron_variant	Intron 4 of 12	ENST00000395066.9	NP_001123500.2	P49761-1B3KRI8
CLK3	NM_003992.5 link	c.466+92G>A		intron_variant	Intron 4 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.466+92G>A		intron_variant	Intron 4 of 12	1	NM_001130028.2	ENSP00000378505.4		P49761-1

Frequencies

GnomAD3 genomes

AF:

0.0454

AC:

6916

AN:

152170

Hom.:

285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0469

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.0448

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0435

Gnomad OTH

AF:

0.0484

GnomAD4 exome

AF:

0.0559

AC:

63035

AN:

1127050

Hom.:

3003

Cov.:

AF XY:

0.0603

AC XY:

34034

AN XY:

564738

show subpopulations

African (AFR)

AF:

0.0129

AC:

342

AN:

26590

American (AMR)

AF:

0.0516

AC:

1882

AN:

36480

Ashkenazi Jewish (ASJ)

AF:

0.0437

AC:

892

AN:

20394

East Asian (EAS)

AF:

0.161

AC:

6002

AN:

37386

South Asian (SAS)

AF:

0.183

AC:

12890

AN:

70400

European-Finnish (FIN)

AF:

0.0438

AC:

2157

AN:

49242

Middle Eastern (MID)

AF:

0.0573

AC:

286

AN:

4994

European-Non Finnish (NFE)

AF:

0.0425

AC:

35409

AN:

833120

Other (OTH)

AF:

0.0655

AC:

3175

AN:

48444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3012

6025

9037

12050

15062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1398

2796

4194

5592

6990

<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:

0.0456

AC:

6942

AN:

152288

Hom.:

291

Cov.:

AF XY:

0.0486

AC XY:

3623

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0142

AC:

589

AN:

41552

American (AMR)

AF:

0.0471

AC:

721

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

932

AN:

5174

South Asian (SAS)

AF:

0.191

AC:

921

AN:

4824

European-Finnish (FIN)

AF:

0.0448

AC:

476

AN:

10626

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0435

AC:

2960

AN:

68020

Other (OTH)

AF:

0.0569

AC:

120

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

330

661

991

1322

1652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0169

Hom.:

Bravo

AF:

0.0415

Asia WGS

AF:

0.242

AC:

840

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

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