NM_001130028.2:c.153-22G>A

Variant names:

• chr15-74619987-G-A
• rs11543198
• NM_001130028.2:c.153-22G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130028.2(CLK3):​c.153-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 1,613,622 control chromosomes in the GnomAD database, including 6,902 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 0.071 (907 hom., cov: 33)
  • Exomes 𝑓: 0.056 (5995 hom.)
• Consequence: CLK3 NM_001130028.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029336512).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130028.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLK3	NM_001130028.2	MANE Select	c.153-22G>A		intron	N/A	NP_001123500.2
	CLK3	NM_003992.5		c.153-22G>A		intron	N/A	NP_003983.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLK3	ENST00000395066.9	TSL:1 MANE Select	c.153-22G>A		intron	N/A	ENSP00000378505.4
	CLK3	ENST00000345005.8	TSL:1	c.153-22G>A		intron	N/A	ENSP00000344112.4
	CLK3	ENST00000568139.6	TSL:5	c.173G>A	p.Arg58His	missense	Exon 3 of 7	ENSP00000455762.2

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10765 AN: 152118 Hom.: 901 Cov.: 33

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0839

GnomAD2 exomes AF: 0.110 AC: 27600 AN: 250566 AF XY: 0.102

Gnomad AFR exome AF: 0.0405

Gnomad AMR exome AF: 0.380

Gnomad ASJ exome AF: 0.0331

Gnomad EAS exome AF: 0.239

Gnomad FIN exome AF: 0.0558

Gnomad NFE exome AF: 0.0327

Gnomad OTH exome AF: 0.0902

GnomAD4 exome AF: 0.0561 AC: 81932 AN: 1461386 Hom.: 5995 Cov.: 31 AF XY: 0.0567 AC XY: 41246 AN XY: 726964

African (AFR) AF: 0.0395 AC: 1321 AN: 33474

American (AMR) AF: 0.368 AC: 16450 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0341 AC: 890 AN: 26130

East Asian (EAS) AF: 0.227 AC: 9001 AN: 39692

South Asian (SAS) AF: 0.115 AC: 9937 AN: 86254

European-Finnish (FIN) AF: 0.0494 AC: 2627 AN: 53186

Middle Eastern (MID) AF: 0.0532 AC: 307 AN: 5766

European-Non Finnish (NFE) AF: 0.0338 AC: 37540 AN: 1111802

Other (OTH) AF: 0.0639 AC: 3859 AN: 60372

GnomAD4 genome AF: 0.0708 AC: 10784 AN: 152236 Hom.: 907 Cov.: 33 AF XY: 0.0766 AC XY: 5700 AN XY: 74430

African (AFR) AF: 0.0415 AC: 1726 AN: 41550

American (AMR) AF: 0.257 AC: 3924 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1224 AN: 5164

South Asian (SAS) AF: 0.117 AC: 566 AN: 4830

European-Finnish (FIN) AF: 0.0592 AC: 628 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0347 AC: 2362 AN: 68024

Other (OTH) AF: 0.0830 AC: 175 AN: 2108

Alfa AF: 0.0525 Hom.: 1514

Bravo AF: 0.0854

TwinsUK AF: 0.0321 AC: 119

ALSPAC AF: 0.0340 AC: 131

ESP6500AA AF: 0.0380 AC: 167

ESP6500EA AF: 0.0345 AC: 296

ExAC AF: 0.0960 AC: 11654

Asia WGS AF: 0.165 AC: 570 AN: 3478

EpiCase AF: 0.0343

EpiControl AF: 0.0343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.0071	T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0029	T
PhyloP100		-0.53
PROVEAN	Benign	-0.41	N
Sift	Uncertain	0.015	D
Sift4G	Benign	0.081	T
GERP RS		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11543198; hg19: chr15-74912328; COSMIC: COSV61412959; COSMIC: COSV61412959;