Genetic Variant CKB:p.Lys177Arg (chr14-103521386-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001823.5(CKB):c.530A>G(p.Lys177Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000051 in 1,608,640 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: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CKB
NM_001823.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.60

Publications

8 publications found

Variant links:

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]

CKB links:

TRMT61A (HGNC:23790): (tRNA methyltransferase 61A) Enables mRNA (adenine-N1-)-methyltransferase activity. Involved in mRNA methylation. Predicted to be located in nucleoplasm. Predicted to be part of tRNA (m1A) methyltransferase complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TRMT61A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKB	NM_001823.5	MANE Select	c.530A>G	p.Lys177Arg	missense	Exon 5 of 8	NP_001814.2
	CKB	NM_001362531.2		c.602A>G	p.Lys201Arg	missense	Exon 4 of 7	NP_001349460.1	A0A0S2Z471

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CKB	ENST00000348956.7	TSL:1 MANE Select	c.530A>G	p.Lys177Arg	missense	Exon 5 of 8	ENSP00000299198.2	P12277
CKB	ENST00000689346.1		c.602A>G	p.Lys201Arg	missense	Exon 4 of 7	ENSP00000508488.1	A0A0S2Z471
CKB	ENST00000955393.1		c.602A>G	p.Lys201Arg	missense	Exon 4 of 7	ENSP00000625452.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000658

AC:

AN:

243012

AF XY:

0.0000831

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000886

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000508

AC:

AN:

1456326

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

724582

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33206

American (AMR)

AF:

0.00

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.00177

AC:

AN:

39584

South Asian (SAS)

AF:

0.00

AC:

AN:

86078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49498

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111254

Other (OTH)

AF:

0.0000498

AC:

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41578

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00154

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000497

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.58

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-0.024

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.79

M_CAP

Benign

0.073

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

5.6

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.91

REVEL

Benign

0.11

Sift

Benign

0.19

Sift4G

Benign

0.42

Polyphen

0.0020

Vest4

0.083

MVP

0.33

MPC

0.80

ClinPred

0.14

GERP RS

4.4

PromoterAI

-0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.43

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.30

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over