chr15-43598839-C-T

Variant names:

• chr15-43598839-C-T
• rs912613433
• NM_001375484.1:c.1024C>T

Variant summary

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

The NM_001375484.1(CKMT1B):​c.1024C>T​(p.Pro342Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,607,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CKMT1B NM_001375484.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.234
• Publications: 0 publications found

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]

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=0.11374751).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375484.1. 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
	CKMT1B	NM_001375484.1	MANE Select	c.1024C>T	p.Pro342Ser	missense	Exon 8 of 9	NP_001362413.1
	CKMT1B	NM_020990.5		c.1024C>T	p.Pro342Ser	missense	Exon 9 of 10	NP_066270.1
	CKMT1B	NR_135748.1		n.2479C>T		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKMT1B	ENST00000441322.6	TSL:1 MANE Select	c.1024C>T	p.Pro342Ser	missense	Exon 8 of 9	ENSP00000413255.2	P12532-1
	CKMT1B	ENST00000882066.1		c.1117C>T	p.Pro373Ser	missense	Exon 9 of 10	ENSP00000552125.1
	CKMT1B	ENST00000300283.10	TSL:5	c.1024C>T	p.Pro342Ser	missense	Exon 9 of 10	ENSP00000300283.6	P12532-1

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 149656 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000759

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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: 0.0000121 AC: 3 AN: 248570 AF XY: 0.0000149

Gnomad AFR exome AF: 0.000189

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458098 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725482

African (AFR) AF: 0.000153 AC: 5 AN: 32708

American (AMR) AF: 0.00 AC: 0 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39006

South Asian (SAS) AF: 0.00 AC: 0 AN: 85884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110952

Other (OTH) AF: 0.00 AC: 0 AN: 60172

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 149656 Hom.: 0 Cov.: 29 AF XY: 0.0000411 AC XY: 3 AN XY: 73022

African (AFR) AF: 0.0000759 AC: 3 AN: 39520

American (AMR) AF: 0.00 AC: 0 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5000

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67926

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.84
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.23
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.86	N
REVEL	Benign	0.039
Sift	Benign	0.77	T
Sift4G	Benign	0.42	T
Vest4		0.24
MutPred		0.31		Gain of MoRF binding (P = 0.0388)
MVP		0.37
MPC		0.86
ClinPred		0.028	T
GERP RS		3.6
gMVP		0.35
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs912613433; hg19: chr15-43891037;