15-43599215-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001375484.1(CKMT1B):c.1196G>A(p.Arg399His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00688 in 1,613,626 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 17 hom., cov: 30)

Exomes 𝑓: 0.0070 ( 174 hom. )

Consequence

CKMT1B
NM_001375484.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

CKMT1B (HGNC:1995): (creatine kinase, mitochondrial 1B) Mitochondrial creatine (MtCK) kinase is responsible for the transfer of high energy phosphate from mitochondria to the cytosolic carrier, creatine. It belongs to the creatine kinase isoenzyme family. It exists as two isoenzymes, sarcomeric MtCK and ubiquitous MtCK, encoded by separate genes. Mitochondrial creatine kinase occurs in two different oligomeric forms: dimers and octamers, in contrast to the exclusively dimeric cytosolic creatine kinase isoenzymes. Many malignant cancers with poor prognosis have shown overexpression of ubiquitous mitochondrial creatine kinase; this may be related to high energy turnover and failure to eliminate cancer cells via apoptosis. Ubiquitous mitochondrial creatine kinase has 80% homology with the coding exons of sarcomeric mitochondrial creatine kinase. Two genes located near each other on chromosome 15 have been identified which encode identical mitochondrial creatine kinase proteins. [provided by RefSeq, Jul 2008]

CKMT1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012996405).

BP6

Variant 15-43599215-G-A is Benign according to our data. Variant chr15-43599215-G-A is described in ClinVar as [Benign]. Clinvar id is 778548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00589 (895/151904) while in subpopulation SAS AF = 0.0219 (105/4802). AF 95% confidence interval is 0.0185. There are 17 homozygotes in GnomAd4. There are 445 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKMT1B	NM_001375484.1 link	c.1196G>A	p.Arg399His	missense_variant	Exon 9 of 9	ENST00000441322.6	NP_001362413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKMT1B	ENST00000441322.6 link	c.1196G>A	p.Arg399His	missense_variant	Exon 9 of 9	1	NM_001375484.1	ENSP00000413255.2		P12532-1

Frequencies

GnomAD3 genomes

AF:

0.00581

AC:

882

AN:

151788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00470

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00446

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0223

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00707

Gnomad OTH

AF:

0.00337

GnomAD2 exomes

AF:

0.00623

AC:

1567

AN:

251408

AF XY:

0.00729

show subpopulations

Gnomad AFR exome

AF:

0.00498

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00665

Gnomad OTH exome

AF:

0.00782

GnomAD4 exome

AF:

0.00698

AC:

10209

AN:

1461722

Hom.:

174

Cov.:

AF XY:

0.00747

AC XY:

5434

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.00394

AC:

132

AN:

33478

Gnomad4 AMR exome

AF:

0.00286

AC:

128

AN:

44720

Gnomad4 ASJ exome

AF:

0.00107

AC:

AN:

26132

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39692

Gnomad4 SAS exome

AF:

0.0190

AC:

1641

AN:

86248

Gnomad4 FIN exome

AF:

0.000637

AC:

AN:

53408

Gnomad4 NFE exome

AF:

0.00701

AC:

7789

AN:

1111894

Gnomad4 Remaining exome

AF:

0.00654

AC:

395

AN:

60386

Heterozygous variant carriers

596

1192

1787

2383

2979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.00589

AC:

895

AN:

151904

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

445

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00505

AC:

0.00504904

AN:

0.00504904

Gnomad4 AMR

AF:

0.00445

AC:

0.00445084

AN:

0.00445084

Gnomad4 ASJ

AF:

0.00173

AC:

0.0017331

AN:

0.0017331

Gnomad4 EAS

AF:

0.000194

AC:

0.000193573

AN:

0.000193573

Gnomad4 SAS

AF:

0.0219

AC:

0.0218659

AN:

0.0218659

Gnomad4 FIN

AF:

0.000284

AC:

0.000283983

AN:

0.000283983

Gnomad4 NFE

AF:

0.00707

AC:

0.0070661

AN:

0.0070661

Gnomad4 OTH

AF:

0.00333

AC:

0.00333016

AN:

0.00333016

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00694

Hom.:

Bravo

AF:

0.00545

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00710

AC:

ExAC

AF:

0.00672

AC:

816

EpiCase

AF:

0.00769

EpiControl

AF:

0.00771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

0.15

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.97

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.048

D;D

Vest4

0.46

MVP

0.44

MPC

1.1

ClinPred

0.029

GERP RS

4.0

gMVP

0.50

Mutation Taster

=71/29

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

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