chr15-43699018-G-A

Variant names:

• chr15-43699018-G-A
• NM_001321926.2:c.1183G>A

Variant summary

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

The NM_001321926.2(CKMT1A):​c.1183G>A​(p.Asp395Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: CKMT1A NM_001321926.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.78
• Publications: 0 publications found

Genes affected

CKMT1A (HGNC:31736): (creatine kinase, mitochondrial 1A) 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321926.2. 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
	CKMT1A	NM_001321926.2	MANE Select	c.1183G>A	p.Asp395Asn	missense	Exon 9 of 9	NP_001308855.1	P12532-1
	CKMT1A	NM_001321927.1		c.1276G>A	p.Asp426Asn	missense	Exon 10 of 10	NP_001308856.1	P12532-2
	CKMT1A	NM_001321928.1		c.1276G>A	p.Asp426Asn	missense	Exon 10 of 10	NP_001308857.1	P12532-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKMT1A	ENST00000413453.7	TSL:1 MANE Select	c.1183G>A	p.Asp395Asn	missense	Exon 9 of 9	ENSP00000406577.3	P12532-1
	CKMT1A	ENST00000909070.1		c.1276G>A	p.Asp426Asn	missense	Exon 10 of 10	ENSP00000579129.1
	CKMT1A	ENST00000909071.1		c.1276G>A	p.Asp426Asn	missense	Exon 10 of 10	ENSP00000579130.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

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
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.1	T
PhyloP100		9.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.23
Sift	Benign	0.049	D
Sift4G	Benign	0.078	T
Vest4		0.36
MutPred		0.47		Gain of catalytic residue at Y392 (P = 0.3049)
MVP		0.41
MPC		0.44
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.58
gMVP		0.47

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

hg19: chr15-43991216;