rs149354459

Variant names:

• chr19-45308434-C-G
• rs149354459
• NM_001824.5:c.752G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-45308434-C-G
• chr19-45308434-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001824.5(CKM):​c.752G>C​(p.Arg251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,614,140 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (12 hom.)
• Consequence: CKM NM_001824.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.537
• Publications: 7 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023885846).
• BP6: Variant 19-45308434-C-G is Benign according to our data. Variant chr19-45308434-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 710253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

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.752G>C	p.Arg251Pro	missense	Exon 6 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.752G>C	p.Arg251Pro	missense	Exon 6 of 8	ENSP00000221476.2	P06732
	CKM	ENST00000969560.1		c.752G>C	p.Arg251Pro	missense	Exon 6 of 8	ENSP00000639619.1
	CKM	ENST00000969562.1		c.869G>C	p.Arg290Pro	missense	Exon 7 of 9	ENSP00000639621.1

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 289 AN: 152168 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00196 AC: 492 AN: 251446 AF XY: 0.00206

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00370

Gnomad NFE exome AF: 0.00280

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.00268 AC: 3925 AN: 1461854 Hom.: 12 Cov.: 33 AF XY: 0.00269 AC XY: 1957 AN XY: 727230

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.000492 AC: 22 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00123 AC: 106 AN: 86258

European-Finnish (FIN) AF: 0.00425 AC: 227 AN: 53420

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00303 AC: 3369 AN: 1111982

Other (OTH) AF: 0.00281 AC: 170 AN: 60392

GnomAD4 genome AF: 0.00190 AC: 289 AN: 152286 Hom.: 0 Cov.: 31 AF XY: 0.00181 AC XY: 135 AN XY: 74452

African (AFR) AF: 0.000650 AC: 27 AN: 41568

American (AMR) AF: 0.000327 AC: 5 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00306 AC: 208 AN: 68030

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00255 Hom.: 0

Bravo AF: 0.00151

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00236 AC: 287

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00255

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Benign	0.067
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.54
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.036	D
Sift4G	Benign	0.099	T
Polyphen		0.033	B
Vest4		0.75
MVP		0.36
MPC		0.47
ClinPred		0.030	T
GERP RS		5.5
Varity_R		0.95
gMVP		0.93
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149354459; hg19: chr19-45811692;