Genetic Variant NM_001130028.2: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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130028.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLK3	NM_001130028.2	MANE Select	c.466+92G>A		intron	N/A	NP_001123500.2
	CLK3	NM_003992.5		c.466+92G>A		intron	N/A	NP_003983.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLK3	ENST00000395066.9	TSL:1 MANE Select	c.466+92G>A	intron	N/A	ENSP00000378505.4
CLK3	ENST00000345005.8	TSL:1	c.466+92G>A	intron	N/A	ENSP00000344112.4
CLK3	ENST00000568605.5	TSL:2	n.585G>A	non_coding_transcript_exon	Exon 4 of 6

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over