19-45306752-A-G

Position:

• chr19-45306752-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_001824.5(CKM):​c.1144T>C​(p.Ter382GlnextTer87) variant causes a stop lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,078 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00097 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (3 hom.)
• Consequence: CKM NM_001824.5 stop_lost
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.92

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 Likely_benign. Variant got -4 ACMG points.

• PM4: Stoplost variant in NM_001824.5 Downstream stopcodon found after 24 codons.
• BP6: Variant 19-45306752-A-G is Benign according to our data. Variant chr19-45306752-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 784717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CKM	NM_001824.5	c.1144T>C	p.Ter382GlnextTer87	stop_lost	8/8	ENST00000221476.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CKM	ENST00000221476.4	c.1144T>C	p.Ter382GlnextTer87	stop_lost	8/8	1	NM_001824.5	P1

Frequencies

GnomAD3 genomes AF: 0.000973 AC: 148 AN: 152152 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000994 AC: 250 AN: 251424 Hom.: 0 AF XY: 0.000854 AC XY: 116 AN XY: 135894

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00347

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00104 AC: 1519 AN: 1461808 Hom.: 3 Cov.: 29 AF XY: 0.000989 AC XY: 719 AN XY: 727214

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.000918

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00442

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.000894

GnomAD4 genome AF: 0.000972 AC: 148 AN: 152270 Hom.: 1 Cov.: 32 AF XY: 0.000967 AC XY: 72 AN XY: 74462

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00116 Hom.: 1

Bravo AF: 0.000699

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000964 AC: 117

EpiCase AF: 0.00120

EpiControl AF: 0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.86
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.98	D
MutationTaster	Benign	1.0	N
Vest4		0.055
GERP RS		5.5

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: rs142092440; hg19: chr19-45810010;