5-81252754-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001099735.2(CKMT2):​c.212C>T​(p.Ala71Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CKMT2
NM_001099735.2 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03
Variant links:
Genes affected
CKMT2 (HGNC:1996): (creatine kinase, mitochondrial 2) Mitochondrial creatine kinase (MtCK) 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. Sarcomeric mitochondrial creatine kinase has 80% homology with the coding exons of ubiquitous mitochondrial creatine kinase. This gene contains sequences homologous to several motifs that are shared among some nuclear genes encoding mitochondrial proteins and thus may be essential for the coordinated activation of these genes during mitochondrial biogenesis. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
CKMT2-AS1 (HGNC:48997): (CKMT2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31022862).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CKMT2NM_001099735.2 linkc.212C>T p.Ala71Val missense_variant Exon 3 of 10 ENST00000254035.9 NP_001093205.1 P17540A0A024RAK5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CKMT2ENST00000254035.9 linkc.212C>T p.Ala71Val missense_variant Exon 3 of 10 1 NM_001099735.2 ENSP00000254035.4 P17540

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.212C>T (p.A71V) alteration is located in exon 4 (coding exon 2) of the CKMT2 gene. This alteration results from a C to T substitution at nucleotide position 212, causing the alanine (A) at amino acid position 71 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;.;T;T;T
Eigen
Benign
-0.094
Eigen_PC
Benign
0.055
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.96
.;D;D;.;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.31
T;T;T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.2
M;.;M;M;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-2.0
N;N;N;N;N
REVEL
Benign
0.094
Sift
Benign
0.045
D;T;D;D;T
Sift4G
Uncertain
0.035
D;T;D;D;T
Polyphen
0.012
B;.;B;B;.
Vest4
0.47
MutPred
0.54
Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP
0.80
MPC
0.34
ClinPred
0.81
D
GERP RS
5.2
Varity_R
0.22
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-80548573; API