Genetic Variant CLK3:c.1-3562G>T (chr15-74615635-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003992.5(CLK3):c.1-3562G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 1,252,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

CLK3
NM_003992.5 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0120

Publications

1 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:

CLK3-AS1 (HGNC:58198):

CLK3-AS1 links:

ENSG00000260919 (HGNC:):

ENSG00000260919 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029238194).

BS2

High AC in GnomAd4 at 89 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003992.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLK3	NM_003992.5		c.1-3562G>T		intron	N/A	NP_003983.2	P49761-1
	CLK3	NM_001130028.2	MANE Select	c.-264G>T		upstream_gene	N/A	NP_001123500.2	P49761-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLK3	ENST00000345005.8	TSL:1	c.1-3562G>T	intron	N/A	ENSP00000344112.4	P49761-1
CLK3	ENST00000969919.1		c.-1+663G>T	intron	N/A	ENSP00000639978.1
CLK3	ENST00000562389.5	TSL:4	c.-1+586G>T	intron	N/A	ENSP00000456399.1	H3BRT8

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00

AC:

AN:

370

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000573

AC:

630

AN:

1099874

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

303

AN XY:

522670

show subpopulations

African (AFR)

AF:

0.0000868

AC:

AN:

23034

American (AMR)

AF:

0.000475

AC:

AN:

8424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14686

East Asian (EAS)

AF:

0.00

AC:

AN:

26516

South Asian (SAS)

AF:

0.0000364

AC:

AN:

27490

European-Finnish (FIN)

AF:

0.00248

AC:

AN:

22570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2980

European-Non Finnish (NFE)

AF:

0.000582

AC:

541

AN:

929786

Other (OTH)

AF:

0.000586

AC:

AN:

44388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<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:

0.000584

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41578

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68012

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000371

Hom.:

Bravo

AF:

0.000480

ExAC

AF:

0.000127

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.34

CADD

Benign

6.7

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0098

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.33

M_CAP

Benign

0.036

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.012

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.59

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0010

Polyphen

0.0010

Vest4

0.26

MVP

0.34

MPC

0.19

ClinPred

0.10

GERP RS

-1.7

PromoterAI

-0.080

Neutral

(source)

Varity_R

0.061

gMVP

0.059

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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