19-45315577-A-G

Position:

• chr19-45315577-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001824.5(CKM):​c.369T>C​(p.Pro123=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CKM	NM_001824.5	c.369T>C	p.Pro123=	synonymous_variant	4/8	ENST00000221476.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CKM	ENST00000221476.4	c.369T>C	p.Pro123=	synonymous_variant	4/8	1	NM_001824.5	P1

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

GnomAD3 exomes AF: 0.531 AC: 128561 AN: 242204 Hom.: 36995 AF XY: 0.550 AC XY: 72348 AN XY: 131522

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 SAS exome AF: 0.584

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

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.584

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.695

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.567

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

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.481

Alfa AF: 0.592 Hom.: 45236

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.0
DANN	Benign	0.43

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