Genetic Variant CKM:p.Pro123Pro (chr19-45315577-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001824.5(CKM):c.369T>C(p.Pro123Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,603,764 control chromosomes in the GnomAD database, including 289,433 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 0.52 ( 22164 hom., cov: 31)

Exomes 𝑓: 0.60 ( 267269 hom. )

Consequence

CKM
NM_001824.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

CKM (HGNC:1994): (creatine kinase, M-type) The protein encoded by this gene is a cytoplasmic enzyme involved in energy homeostasis and is an important serum marker for myocardial infarction. The encoded protein reversibly catalyzes the transfer of phosphate between ATP and various phosphogens such as creatine phosphate. It acts as a homodimer in striated muscle as well as in other tissues, and as a heterodimer with a similar brain isozyme in heart. The encoded protein is a member of the ATP:guanido phosphotransferase protein family. [provided by RefSeq, Jul 2008]

CKM links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP7

Synonymous conserved (PhyloP=1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKM	NM_001824.5 link	c.369T>C	p.Pro123Pro	synonymous_variant	Exon 4 of 8	ENST00000221476.4	NP_001815.2	P06732B2R892

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKM	ENST00000221476.4 link	c.369T>C	p.Pro123Pro	synonymous_variant	Exon 4 of 8	1	NM_001824.5	ENSP00000221476.2		P06732

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78797

AN:

151828

Hom.:

22148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.799

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.576

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.479

GnomAD2 exomes

AF:

0.531

AC:

128561

AN:

242204

AF XY:

0.550

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.593

Gnomad EAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.703

Gnomad NFE exome

AF:

0.630

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.598

AC:

868342

AN:

1451818

Hom.:

267269

Cov.:

AF XY:

0.600

AC XY:

433592

AN XY:

722550

show subpopulations

Gnomad4 AFR exome

AF:

0.333

AC:

11151

AN:

33472

Gnomad4 AMR exome

AF:

0.326

AC:

14588

AN:

44708

Gnomad4 ASJ exome

AF:

0.584

AC:

15251

AN:

26134

Gnomad4 EAS exome

AF:

0.201

AC:

7984

AN:

39694

Gnomad4 SAS exome

AF:

0.587

AC:

50595

AN:

86246

Gnomad4 FIN exome

AF:

0.695

AC:

30305

AN:

43608

Gnomad4 NFE exome

AF:

0.631

AC:

701417

AN:

1111870

Gnomad4 Remaining exome

AF:

0.567

AC:

34210

AN:

60320

Heterozygous variant carriers

20608

41216

61824

82432

103040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

18312

36624

54936

73248

91560

<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:

0.519

AC:

78848

AN:

151946

Hom.:

22164

Cov.:

AF XY:

0.519

AC XY:

38530

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.346

AC:

0.346469

AN:

0.346469

Gnomad4 AMR

AF:

0.389

AC:

0.388969

AN:

0.388969

Gnomad4 ASJ

AF:

0.583

AC:

0.582757

AN:

0.582757

Gnomad4 EAS

AF:

0.231

AC:

0.231442

AN:

0.231442

Gnomad4 SAS

AF:

0.577

AC:

0.57662

AN:

0.57662

Gnomad4 FIN

AF:

0.711

AC:

0.710531

AN:

0.710531

Gnomad4 NFE

AF:

0.636

AC:

0.635589

AN:

0.635589

Gnomad4 OTH

AF:

0.481

AC:

0.481446

AN:

0.481446

Heterozygous variant carriers

1791

3582

5372

7163

8954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.584

Hom.:

97723

Bravo

AF:

0.482

Asia WGS

AF:

0.426

AC:

1487

AN:

3478

EpiCase

AF:

0.624

EpiControl

AF:

0.616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.0

DANN

Benign

0.43

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over