Variant 15-74619341-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001130028.2(CLK3):c.145T>C(p.Ser49Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,774 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLK3
NM_001130028.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.09

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31543761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLK3	NM_001130028.2 linkuse as main transcript	c.145T>C	p.Ser49Pro	missense_variant	2/13	ENST00000395066.9
CLK3	NM_003992.5 linkuse as main transcript	c.145T>C	p.Ser49Pro	missense_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLK3	ENST00000395066.9 linkuse as main transcript	c.145T>C	p.Ser49Pro	missense_variant	2/13	1	NM_001130028.2	P1	P49761-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.589T>C (p.S197P) alteration is located in exon 2 (coding exon 2) of the CLK3 gene. This alteration results from a T to C substitution at nucleotide position 589, causing the serine (S) at amino acid position 197 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

0.0080

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

.;T;T;T;T;T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.68

T;T;T;T;T;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.32

T;T;T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.81

.;.;L;.;.;.;.

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.011

D;D;D;D;D;D;D

Sift4G

Benign

0.13

T;T;D;T;T;D;T

Polyphen

0.99

.;.;D;.;.;.;.

Vest4

0.61

MutPred

0.33

.;.;Loss of phosphorylation at S197 (P = 2e-04);.;.;.;.;

MVP

0.50

MPC

0.75

ClinPred

0.86

GERP RS

4.7

Varity_R

0.28

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over