rs13558

Variant names:

• chr14-103520290-T-C
• rs13558
• NM_001823.5:c.799A>G

Variant summary

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

The NM_001823.5(CKB):​c.799A>G​(p.Lys267Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CKB NM_001823.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 4 publications found

Genes affected

CKB (HGNC:1991): (creatine kinase B) The protein encoded by this gene is a cytoplasmic enzyme involved in energy homeostasis. The encoded protein reversibly catalyzes the transfer of phosphate between ATP and various phosphogens such as creatine phosphate. It acts as a homodimer in brain as well as in other tissues, and as a heterodimer with a similar muscle isozyme in heart. The encoded protein is a member of the ATP:guanido phosphotransferase protein family. A pseudogene of this gene has been characterized. [provided by RefSeq, Jul 2008]

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=0.2334347).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001823.5. 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
	CKB	NM_001823.5	MANE Select	c.799A>G	p.Lys267Glu	missense	Exon 7 of 8	NP_001814.2
	CKB	NM_001362531.2		c.871A>G	p.Lys291Glu	missense	Exon 6 of 7	NP_001349460.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKB	ENST00000348956.7	TSL:1 MANE Select	c.799A>G	p.Lys267Glu	missense	Exon 7 of 8	ENSP00000299198.2
	CKB	ENST00000689346.1		c.871A>G	p.Lys291Glu	missense	Exon 6 of 7	ENSP00000508488.1
	CKB	ENST00000553610.5	TSL:3	c.193A>G	p.Lys65Glu	missense	Exon 3 of 4	ENSP00000451426.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.084
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Benign	0.49	T
Sift4G	Benign	0.33	T
Polyphen		0.19	B
Vest4		0.51
MutPred		0.44		Gain of catalytic residue at E270 (P = 0.0159)
MVP		0.23
MPC		1.8
ClinPred		0.82	D
GERP RS		4.8
Varity_R		0.68
gMVP		0.82
Mutation Taster		=78/22	polymorphism

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: rs13558; hg19: chr14-103986627;