chr15-43596261-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001375484.1(CKMT1B):​c.721G>A​(p.Ala241Thr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CKMT1B NM_001375484.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.74

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKMT1B	NM_001375484.1	c.721G>A	p.Ala241Thr	missense_variant	Exon 5 of 9	ENST00000441322.6	NP_001362413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKMT1B	ENST00000441322.6	c.721G>A	p.Ala241Thr	missense_variant	Exon 5 of 9	1	NM_001375484.1	ENSP00000413255.2

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome AF: 0.00000169 AC: 1 AN: 591898 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 306840

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000256

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;.;.;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.;.;.
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-0.70	T
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.2	D;D;D;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;D;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Vest4		0.67, 0.67, 0.68
MutPred		0.67		Gain of phosphorylation at A241 (P = 0.0657);Gain of phosphorylation at A241 (P = 0.0657);Gain of phosphorylation at A241 (P = 0.0657);Gain of phosphorylation at A241 (P = 0.0657);
MVP		0.69
MPC		0.90
ClinPred		0.99	D
GERP RS		4.3
gMVP		0.74

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

Other links and lift over

dbSNP: rs747668618; hg19: chr15-43888459;