rs2062048351

Variant names:

• chr15-74615642-G-A
• rs2062048351
• ENST00000345005.8:c.1-3555G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-74615642-G-A
• chr15-74615642-G-C
• chr15-74615642-G-T

Variant summary

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

The NM_003992.5(CLK3):​c.1-3555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,714 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CLK3 NM_003992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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):

ENSG00000260919 (HGNC:):

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=0.072211325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLK3	NM_003992.5	c.1-3555G>A		intron_variant	Intron 1 of 12		NP_003983.2
CLK3-AS1	XR_007064714.1	n.151C>T		non_coding_transcript_exon_variant	Exon 1 of 12
CLK3-AS1	XR_007064715.1	n.151C>T		non_coding_transcript_exon_variant	Exon 1 of 9
CLK3	NM_001130028.2	c.-257G>A		upstream_gene_variant		ENST00000395066.9	NP_001123500.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLK3	ENST00000395066.9	c.-257G>A		upstream_gene_variant		1	NM_001130028.2	ENSP00000378505.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1098714 Hom.: 0 Cov.: 30 AF XY: 0.00000192 AC XY: 1 AN XY: 521942

African (AFR) AF: 0.00 AC: 0 AN: 23010

American (AMR) AF: 0.00 AC: 0 AN: 8422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14678

East Asian (EAS) AF: 0.00 AC: 0 AN: 26514

South Asian (SAS) AF: 0.0000370 AC: 1 AN: 27002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2980

European-Non Finnish (NFE) AF: 0.00000215 AC: 2 AN: 929346

Other (OTH) AF: 0.00 AC: 0 AN: 44318

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.0
DANN	Benign	0.77
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.010	N
Sift	Benign	0.030	D
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.088
MutPred		0.20		Gain of stability (P = 0.0106);
MVP		0.24
MPC		0.21
ClinPred		0.11	T
GERP RS		-0.43
PromoterAI		-0.038	Neutral
Varity_R		0.069
gMVP		0.055

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

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Other links and lift over

dbSNP: rs2062048351; hg19: chr15-74907983;