chr15-74615864-A-C

Variant names:

• chr15-74615864-A-C
• NM_001130028.2:c.-35A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130028.2(CLK3):​c.-35A>C variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLK3 NM_001130028.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.430
• Publications: 0 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]

CLK3-AS1 (HGNC:58198):

ACMG classification

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=0.14695969).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLK3	NM_001130028.2	MANE Select	c.-35A>C		5_prime_UTR	Exon 1 of 13	NP_001123500.2	P49761-1
	CLK3	NM_003992.5		c.1-3333A>C		intron	N/A	NP_003983.2	P49761-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLK3	ENST00000395066.9	TSL:1 MANE Select	c.-35A>C		5_prime_UTR	Exon 1 of 13	ENSP00000378505.4	P49761-1
	CLK3	ENST00000345005.8	TSL:1	c.1-3333A>C		intron	N/A	ENSP00000344112.4	P49761-1
	CLK3	ENST00000899327.1		c.-35A>C		5_prime_UTR	Exon 1 of 14	ENSP00000569386.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.43
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.33	N
Sift	Uncertain	0.025	D
Sift4G	Benign	0.25	T
Polyphen		0.015	B
Vest4		0.14
MutPred		0.28		Gain of loop (P = 0.0013)
MVP		0.44
MPC		0.17
ClinPred		0.48	T
GERP RS		2.4
PromoterAI		-0.080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
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

Other links and lift over

hg19: chr15-74908205;