Variant 19-45315567-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001824.5(CKM):c.379C>G(p.Leu127Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,604,350 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 14 hom. )

Consequence

CKM
NM_001824.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019913375).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CKM	NM_001824.5 linkuse as main transcript	c.379C>G	p.Leu127Val	missense_variant	4/8	ENST00000221476.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CKM	ENST00000221476.4 linkuse as main transcript	c.379C>G	p.Leu127Val	missense_variant	4/8	1	NM_001824.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

355

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00328

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00320

AC:

777

AN:

242458

Hom.:

AF XY:

0.00368

AC XY:

485

AN XY:

131664

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00557

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.00369

Gnomad FIN exome

AF:

0.00277

Gnomad NFE exome

AF:

0.00438

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00293

AC:

4251

AN:

1452048

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

2218

AN XY:

722632

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00582

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00383

Gnomad4 FIN exome

AF:

0.00354

Gnomad4 NFE exome

AF:

0.00294

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

AF:

0.00233

AC:

355

AN:

152302

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00328

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00268

Hom.:

Bravo

AF:

0.00216

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00368

AC:

447

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00451

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.29

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0084

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.090

Sift

Benign

0.11

Sift4G

Benign

0.41

Polyphen

0.0030

Vest4

0.63

MVP

0.17

MPC

0.34

ClinPred

0.030

GERP RS

0.085

Varity_R

0.23

gMVP

0.52

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over