Genetic Variant CMPK1:p.Gly8Arg (chr1-47333967-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016308.3(CMPK1):c.22G>C(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,491,702 control chromosomes in the GnomAD database, including 195,300 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 26009 hom., cov: 31)

Exomes 𝑓: 0.50 ( 169291 hom. )

Consequence

CMPK1
NM_016308.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490

Publications

39 publications found

Variant links:

Genes affected

CMPK1 (HGNC:18170): (cytidine/uridine monophosphate kinase 1) This gene encodes one of the enzymes required for cellular nucleic acid biosynthesis. This enzyme catalyzes the transfer of a phosphate group from ATP to CMP, UMP, or dCMP, to form the corresponding diphosphate nucleotide. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Feb 2012]

CMPK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.0106025E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMPK1	NM_016308.3 link	c.22G>C	p.Gly8Arg	missense_variant	Exon 1 of 6	ENST00000371873.10	NP_057392.1	P30085-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMPK1	ENST00000371873.10 link	c.22G>C	p.Gly8Arg	missense_variant	Exon 1 of 6	1	NM_016308.3	ENSP00000360939.5		P30085-3

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

85692

AN:

150844

Hom.:

25980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.789

Gnomad AMI

AF:

0.534

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.536

GnomAD2 exomes

AF:

0.472

AC:

70933

AN:

150196

AF XY:

0.465

show subpopulations

Gnomad AFR exome

AF:

0.782

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.562

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.457

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.498

AC:

667545

AN:

1340750

Hom.:

169291

Cov.:

AF XY:

0.495

AC XY:

328840

AN XY:

664930

show subpopulations

African (AFR)

AF:

0.801

AC:

22226

AN:

27754

American (AMR)

AF:

0.552

AC:

19089

AN:

34594

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

8324

AN:

22888

East Asian (EAS)

AF:

0.616

AC:

18906

AN:

30716

South Asian (SAS)

AF:

0.466

AC:

34391

AN:

73724

European-Finnish (FIN)

AF:

0.360

AC:

17064

AN:

47344

Middle Eastern (MID)

AF:

0.476

AC:

1792

AN:

3762

European-Non Finnish (NFE)

AF:

0.496

AC:

518696

AN:

1046006

Other (OTH)

AF:

0.501

AC:

27057

AN:

53962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

17749

35497

53246

70994

88743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.568

AC:

85762

AN:

150952

Hom.:

26009

Cov.:

AF XY:

0.562

AC XY:

41442

AN XY:

73708

show subpopulations

African (AFR)

AF:

0.789

AC:

32662

AN:

41384

American (AMR)

AF:

0.565

AC:

8582

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1202

AN:

3454

East Asian (EAS)

AF:

0.583

AC:

2970

AN:

5096

South Asian (SAS)

AF:

0.453

AC:

2182

AN:

4812

European-Finnish (FIN)

AF:

0.356

AC:

3616

AN:

10158

Middle Eastern (MID)

AF:

0.462

AC:

135

AN:

292

European-Non Finnish (NFE)

AF:

0.486

AC:

32814

AN:

67564

Other (OTH)

AF:

0.532

AC:

1115

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1747

3494

5240

6987

8734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.439

Hom.:

4104

Bravo

AF:

0.595

TwinsUK

AF:

0.497

AC:

1843

ALSPAC

AF:

0.499

AC:

1925

ESP6500AA

AF:

0.762

AC:

3307

ESP6500EA

AF:

0.470

AC:

4001

ExAC

AF:

0.443

AC:

50962

Asia WGS

AF:

0.503

AC:

1708

AN:

3390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.1

(source)

DANN

Benign

0.29

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.16

T;T;T

MetaRNN

Benign

8.0e-7

T;T;T

MetaSVM

Benign

-0.95

PhyloP100

0.049

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.16

N;N;N

REVEL

Benign

0.056

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.72

T;T;T

Vest4

0.23

MutPred

0.36

Gain of MoRF binding (P = 0.0023);Gain of MoRF binding (P = 0.0023);Gain of MoRF binding (P = 0.0023);

MPC

1.2

ClinPred

0.0027

GERP RS

2.9

PromoterAI

-0.0087

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.30

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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1-47333967-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over