chr19-45306777-A-C

Variant names:

• chr19-45306777-A-C
• rs4884
• NM_001824.5:c.1119T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001824.5(CKM):​c.1119T>G​(p.Ile373Met) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CKM NM_001824.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654
• Publications: 0 publications found

Genes affected

CKM (HGNC:1994): (creatine kinase, M-type) The protein encoded by this gene is a cytoplasmic enzyme involved in energy homeostasis and is an important serum marker for myocardial infarction. The encoded protein reversibly catalyzes the transfer of phosphate between ATP and various phosphogens such as creatine phosphate. It acts as a homodimer in striated muscle as well as in other tissues, and as a heterodimer with a similar brain isozyme in heart. The encoded protein is a member of the ATP:guanido phosphotransferase protein family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKM	NM_001824.5	c.1119T>G	p.Ile373Met	missense_variant	Exon 8 of 8	ENST00000221476.4	NP_001815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKM	ENST00000221476.4	c.1119T>G	p.Ile373Met	missense_variant	Exon 8 of 8	1	NM_001824.5	ENSP00000221476.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.089	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		0.65
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.96	D
Vest4		0.71
MutPred		0.45		Loss of helix (P = 0.1299);
MVP		0.35
MPC		0.85
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.80
gMVP		0.52
Mutation Taster		=78/22	polymorphism

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: rs4884; hg19: chr19-45810035;