Variant 15-74615635-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000345005.8(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
ENST00000345005.8 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0120

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:

LOC102723750 (HGNC:):

LOC102723750 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High AC in GnomAd at 89 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
LOC102723750	XR_007064714.1 linkuse as main transcript	n.158C>A	non_coding_transcript_exon_variant	1/12
CLK3	NM_003992.5 linkuse as main transcript	c.1-3562G>T	intron_variant
LOC102723750	XR_007064715.1 linkuse as main transcript	n.158C>A	non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Appris	UniProt
CLK3	ENST00000345005.8 linkuse as main transcript	c.1-3562G>T	intron_variant	1	P1	P49761-1
CLK3	ENST00000562389.5 linkuse as main transcript	c.-1+586G>T	intron_variant	4
CLK3	ENST00000483723.5 linkuse as main transcript	c.1-3562G>T	intron_variant, NMD_transcript_variant	2		P49761-2
	ENST00000565737.1 linkuse as main transcript		upstream_gene_variant	5

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

GnomAD4 exome

AF:

0.000573

AC:

630

AN:

1099874

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

303

AN XY:

522670

show subpopulations

Gnomad4 AFR exome

AF:

0.0000868

Gnomad4 AMR exome

AF:

0.000475

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000364

Gnomad4 FIN exome

AF:

0.00248

Gnomad4 NFE exome

AF:

0.000582

Gnomad4 OTH exome

AF:

0.000586

GnomAD4 genome

AF:

0.000584

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000371

Hom.:

Bravo

AF:

0.000480

ExAC

AF:

0.000127

AC:

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

Oct 06, 2021

The c.181G>T (p.G61W) alteration is located in exon 1 (coding exon 1) of the CLK3 gene. This alteration results from a G to T substitution at nucleotide position 181, causing the glycine (G) at amino acid position 61 to be replaced by a tryptophan (W). 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

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.34

Cadd

Benign

6.7

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

MutationTaster

Benign

1.0

N;N

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

Varity_R

0.061

gMVP

0.059

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