Genetic Variant CLK3:c.1-3562G>A (chr15-74615635-G-A) – 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>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,252,080 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CLK3
NM_003992.5 intron

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.044591635).

BS2

High AC in GnomAdExome4 at 12 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>A		intron	N/A	NP_003983.2	P49761-1
	CLK3	NM_001130028.2	MANE Select	c.-264G>A		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>A	intron	N/A	ENSP00000344112.4	P49761-1
CLK3	ENST00000969919.1		c.-1+663G>A	intron	N/A	ENSP00000639978.1
CLK3	ENST00000562389.5	TSL:4	c.-1+586G>A	intron	N/A	ENSP00000456399.1	H3BRT8

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1099874

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

522670

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23034

American (AMR)

AF:

0.00

AC:

AN:

8424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14686

East Asian (EAS)

AF:

0.0000377

AC:

AN:

26516

South Asian (SAS)

AF:

0.00

AC:

AN:

27490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2980

European-Non Finnish (NFE)

AF:

0.0000118

AC:

AN:

929786

Other (OTH)

AF:

0.00

AC:

AN:

44388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.2

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0073

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.38

M_CAP

Benign

0.021

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.012

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.010

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0030

Polyphen

0.0010

Vest4

0.098

MutPred

0.19

Gain of MoRF binding (P = 0.0244)

MVP

0.22

MPC

0.19

ClinPred

0.10

GERP RS

-1.7

PromoterAI

0.0037

Neutral

(source)

Varity_R

0.060

gMVP

0.039

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