NM_001824.5:c.369T>C

Variant names:

• chr19-45315577-A-G
• rs1133190
• NM_001824.5:c.369T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001824.5(CKM):​c.369T>C​(p.Pro123Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,603,764 control chromosomes in the GnomAD database, including 289,433 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (22164 hom., cov: 31)
  • Exomes 𝑓: 0.60 (267269 hom.)
• Consequence: CKM NM_001824.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 16 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001824.5. 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
	CKM	NM_001824.5	MANE Select	c.369T>C	p.Pro123Pro	synonymous	Exon 4 of 8	NP_001815.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKM	ENST00000221476.4	TSL:1 MANE Select	c.369T>C	p.Pro123Pro	synonymous	Exon 4 of 8	ENSP00000221476.2
	CKM	ENST00000969560.1		c.369T>C	p.Pro123Pro	synonymous	Exon 4 of 8	ENSP00000639619.1
	CKM	ENST00000969562.1		c.369T>C	p.Pro123Pro	synonymous	Exon 4 of 9	ENSP00000639621.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78797 AN: 151828 Hom.: 22148 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.479

GnomAD2 exomes AF: 0.531 AC: 128561 AN: 242204 AF XY: 0.550

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.319

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.231

Gnomad FIN exome AF: 0.703

Gnomad NFE exome AF: 0.630

Gnomad OTH exome AF: 0.543

GnomAD4 exome AF: 0.598 AC: 868342 AN: 1451818 Hom.: 267269 Cov.: 64 AF XY: 0.600 AC XY: 433592 AN XY: 722550

African (AFR) AF: 0.333 AC: 11151 AN: 33472

American (AMR) AF: 0.326 AC: 14588 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 15251 AN: 26134

East Asian (EAS) AF: 0.201 AC: 7984 AN: 39694

South Asian (SAS) AF: 0.587 AC: 50595 AN: 86246

European-Finnish (FIN) AF: 0.695 AC: 30305 AN: 43608

Middle Eastern (MID) AF: 0.493 AC: 2841 AN: 5766

European-Non Finnish (NFE) AF: 0.631 AC: 701417 AN: 1111870

Other (OTH) AF: 0.567 AC: 34210 AN: 60320

GnomAD4 genome AF: 0.519 AC: 78848 AN: 151946 Hom.: 22164 Cov.: 31 AF XY: 0.519 AC XY: 38530 AN XY: 74256

African (AFR) AF: 0.346 AC: 14357 AN: 41438

American (AMR) AF: 0.389 AC: 5938 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2021 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1191 AN: 5146

South Asian (SAS) AF: 0.577 AC: 2777 AN: 4816

European-Finnish (FIN) AF: 0.711 AC: 7516 AN: 10578

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43173 AN: 67926

Other (OTH) AF: 0.481 AC: 1012 AN: 2102

Alfa AF: 0.584 Hom.: 97723

Bravo AF: 0.482

Asia WGS AF: 0.426 AC: 1487 AN: 3478

EpiCase AF: 0.624

EpiControl AF: 0.616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.0
DANN	Benign	0.43
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs1133190; hg19: chr19-45818835; COSMIC: COSV55532259;