15-43596261-G-T

Variant names:

• chr15-43596261-G-T
• rs747668618
• NM_001375484.1:c.721G>T

Variant summary

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

The NM_001375484.1(CKMT1B):​c.721G>T​(p.Ala241Ser) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CKMT1B NM_001375484.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.74
• 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.

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.721G>T	p.Ala241Ser	missense	Exon 5 of 9	NP_001362413.1
	CKMT1B	NM_020990.5		c.721G>T	p.Ala241Ser	missense	Exon 6 of 10	NP_066270.1
	CKMT1B	NR_135748.1		n.1359G>T		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKMT1B	ENST00000441322.6	TSL:1 MANE Select	c.721G>T	p.Ala241Ser	missense	Exon 5 of 9	ENSP00000413255.2	P12532-1
	CKMT1B	ENST00000882066.1		c.814G>T	p.Ala272Ser	missense	Exon 6 of 10	ENSP00000552125.1
	CKMT1B	ENST00000300283.10	TSL:5	c.721G>T	p.Ala241Ser	missense	Exon 6 of 10	ENSP00000300283.6	P12532-1

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD2 exomes AF: 0.0000126 AC: 1 AN: 79538 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000319

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000135 AC: 8 AN: 591898 Hom.: 0 Cov.: 8 AF XY: 0.0000130 AC XY: 4 AN XY: 306840

African (AFR) AF: 0.00 AC: 0 AN: 15008

American (AMR) AF: 0.00 AC: 0 AN: 24328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15574

East Asian (EAS) AF: 0.00 AC: 0 AN: 30150

South Asian (SAS) AF: 0.00 AC: 0 AN: 50814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2334

European-Non Finnish (NFE) AF: 0.0000179 AC: 7 AN: 391240

Other (OTH) AF: 0.0000326 AC: 1 AN: 30676

GnomAD4 genome Cov.: 8

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000113 AC: 1

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	-0.15	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
PhyloP100		7.7
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.22
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.026	D
Vest4		0.54
MutPred		0.70		Gain of disorder (P = 0.0701)
MVP		0.45
MPC		0.87
ClinPred		0.67	D
GERP RS		4.3
gMVP		0.63

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

Other links and lift over

dbSNP: rs747668618; hg19: chr15-43888459;