Genetic Variant CLK3:c.1-3520C>A (chr15-74615677-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003992.5(CLK3):c.1-3520C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLK3
NM_003992.5 intron

Scores

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07035193).

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

352

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1089834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

516322

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:

0.00

AC:

AN:

924838

Other (OTH)

AF:

0.00

AC:

AN:

43998

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.36

M_CAP

Benign

0.058

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

-0.25

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.040

Sift

Pathogenic

0.0

Sift4G

Benign

0.24

Polyphen

0.032

Vest4

0.13

MutPred

0.12

Gain of MoRF binding (P = 0.0968)

MVP

0.30

MPC

0.17

ClinPred

0.23

GERP RS

1.7

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.14

gMVP

0.028

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over