Genetic Variant CMPK1:p.Gly8Trp (chr1-47333967-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000371873.10(CMPK1):c.22G>T(p.Gly8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000134 in 1,493,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

CMPK1
ENST00000371873.10 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12225768).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371873.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CMPK1	NM_016308.3	MANE Select	c.22G>T	p.Gly8Trp	missense	Exon 1 of 6	NP_057392.1
CMPK1	NM_001366135.1		c.-75G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001353064.1
CMPK1	NM_001136140.2		c.22G>T	p.Gly8Trp	missense	Exon 1 of 5	NP_001129612.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CMPK1	ENST00000371873.10	TSL:1 MANE Select	c.22G>T	p.Gly8Trp	missense	Exon 1 of 6	ENSP00000360939.5
CMPK1	ENST00000699074.1		c.-75G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000514113.1
CMPK1	ENST00000699075.1		c.-75G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000514114.1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.45e-7

AC:

AN:

1342244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27766

American (AMR)

AF:

0.00

AC:

AN:

34724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22920

East Asian (EAS)

AF:

0.00

AC:

AN:

30804

South Asian (SAS)

AF:

0.00

AC:

AN:

73900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3770

European-Non Finnish (NFE)

AF:

9.55e-7

AC:

AN:

1046872

Other (OTH)

AF:

0.00

AC:

AN:

54030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73638

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41278

American (AMR)

AF:

0.00

AC:

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67610

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

4104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.80

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.17

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.92

PhyloP100

0.049

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.61

REVEL

Benign

0.11

Sift

Benign

0.10

Sift4G

Benign

0.16

Vest4

0.20

MutPred

0.45

Loss of disorder (P = 0.0091)

MVP

0.15

MPC

1.2

ClinPred

0.88

GERP RS

2.9

PromoterAI

-0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.39

Mutation Taster

=94/6

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over