Variant 1-47373075-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016308.3(CMPK1):c.439T>C(p.Ser147Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CMPK1
NM_016308.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

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:

CMPK1 (HGNC:):

CMPK1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMPK1	NM_016308.3 linkuse as main transcript	c.439T>C	p.Ser147Pro	missense_variant	3/6	ENST00000371873.10	NP_057392.1	P30085-3
CMPK1	NM_001366135.1 linkuse as main transcript	c.343T>C	p.Ser115Pro	missense_variant	3/6		NP_001353064.1
CMPK1	NM_001136140.2 linkuse as main transcript	c.292T>C	p.Ser98Pro	missense_variant	2/5		NP_001129612.1	P30085A0A494BXC7
CMPK1	NR_046394.2 linkuse as main transcript	n.595T>C		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMPK1	ENST00000371873.10 linkuse as main transcript	c.439T>C	p.Ser147Pro	missense_variant	3/6	1	NM_016308.3	ENSP00000360939.5		P30085-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248248

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000209

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1456706

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724688

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.292T>C (p.S98P) alteration is located in exon 2 (coding exon 2) of the CMPK1 gene. This alteration results from a T to C substitution at nucleotide position 292, causing the serine (S) at amino acid position 98 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.68

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.075

T;T

Sift4G

Benign

0.13

T;T

Vest4

0.62

MutPred

0.64

Loss of ubiquitination at K143 (P = 0.1296);.;

MVP

0.77

MPC

1.3

ClinPred

0.12

GERP RS

-0.25

gMVP

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over