Genetic Variant CLK3:c.1-3520C>T (chr15-74615677-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003992.5(CLK3):c.1-3520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000242 in 1,242,016 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Consequence

CLK3
NM_003992.5 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.252

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06446192).

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.1-3520C>T		intron	N/A	NP_003983.2	P49761-1
	CLK3	NM_001130028.2	MANE Select	c.-222C>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.1-3520C>T	intron	N/A	ENSP00000344112.4	P49761-1
CLK3	ENST00000969919.1		c.-1+705C>T	intron	N/A	ENSP00000639978.1
CLK3	ENST00000562389.5	TSL:4	c.-1+628C>T	intron	N/A	ENSP00000456399.1	H3BRT8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.18e-7

AC:

AN:

1089834

Hom.:

Cov.:

AF XY:

0.00000194

AC XY:

AN XY:

516322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22972

American (AMR)

AF:

0.00

AC:

AN:

8412

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14548

East Asian (EAS)

AF:

0.00

AC:

AN:

26498

South Asian (SAS)

AF:

0.00

AC:

AN:

23802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2944

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

924838

Other (OTH)

AF:

0.00

AC:

AN:

43998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00000756

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

0.076

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

8.5

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.40

M_CAP

Benign

0.079

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

-0.25

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.21

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

0.0

Vest4

0.049

MutPred

0.11

Loss of glycosylation at S74 (P = 0.067)

MVP

0.26

MPC

0.17

ClinPred

0.22

GERP RS

1.7

PromoterAI

-0.0022

Neutral

(source)

Varity_R

0.13

gMVP

0.046

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