rs56298217

chr15-74622308-G-Achr15-74622308-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001130028.2(CLK3):c.466+92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,279,338 control chromosomes in the GnomAD database, including 3,294 homozygotes. 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 0.046 (291 hom., cov: 33)
  • Exomes 𝑓: 0.056 (3003 hom.)
• Consequence: CLK3 NM_001130028.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLK3	NM_001130028.2	c.466+92G>A		intron_variant		ENST00000395066.9
CLK3	NM_003992.5	c.466+92G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLK3	ENST00000395066.9	c.466+92G>A		intron_variant		1	NM_001130028.2	P1

Frequencies

GnomAD3 genomes AF: 0.0454 AC: 6916 AN: 152170 Hom.: 285 Cov.: 33

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.0484

GnomAD4 exome AF: 0.0559 AC: 63035 AN: 1127050 Hom.: 3003 Cov.: 15 AF XY: 0.0603 AC XY: 34034 AN XY: 564738

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.0516

Gnomad4 ASJ exome AF: 0.0437

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.0438

Gnomad4 NFE exome AF: 0.0425

Gnomad4 OTH exome AF: 0.0655

GnomAD4 genome AF: 0.0456 AC: 6942 AN: 152288 Hom.: 291 Cov.: 33 AF XY: 0.0486 AC XY: 3623 AN XY: 74472

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.0435

Gnomad4 OTH AF: 0.0569

Alfa AF: 0.0169 Hom.: 10

Bravo AF: 0.0415

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	22
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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

Other links and lift over

dbSNP: rs56298217; hg19: chr15-74914649; COSMIC: COSV61411997; COSMIC: COSV61411997;