Variant X-16678424-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_175859.3(CTPS2):c.1032G>C(p.Lys344Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,198,558 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

CTPS2
NM_175859.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.104

Variant links:

Genes affected

CTPS2 (HGNC:2520): (CTP synthase 2) The protein encoded by this gene catalyzes the formation of CTP from UTP with the concomitant deamination of glutamine to glutamate. This protein is the rate-limiting enzyme in the synthesis of cytosine nucleotides, which play an important role in various metabolic processes and provide the precursors necessary for the synthesis of RNA and DNA. Cancer cells that exhibit increased cell proliferation also exhibit an increased activity of this encoded protein. Thus, this protein is an attractive target for selective chemotherapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

CTPS2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0838604).

BP6

Variant X-16678424-C-G is Benign according to our data. Variant chrX-16678424-C-G is described in ClinVar as [Benign]. Clinvar id is 1339648.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTPS2	NM_175859.3 linkuse as main transcript	c.1032G>C	p.Lys344Asn	missense_variant	10/19	ENST00000359276.9	NP_787055.1	Q9NRF8A0A024RC00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTPS2	ENST00000359276.9 linkuse as main transcript	c.1032G>C	p.Lys344Asn	missense_variant	10/19	1	NM_175859.3	ENSP00000352222.4	Q9NRF8
CTPS2	ENST00000380241.7 linkuse as main transcript	c.1032G>C	p.Lys344Asn	missense_variant	10/19	1		ENSP00000369590.3	Q9NRF8
CTPS2	ENST00000443824.5 linkuse as main transcript	c.1032G>C	p.Lys344Asn	missense_variant	10/19	2		ENSP00000401264.1	Q9NRF8

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111587

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33751

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.20e-7

AC:

AN:

1086971

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

353141

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111587

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33751

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CYTIDINE 5-PRIME TRIPHOSPHATE SYNTHETASE 2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomics Facility, Ludwig-Maximilians-Universität München

Feb 08, 2022

The variant was identified as hemizygouse in an adult, healthy male. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.4

DANN

Benign

0.79

DEOGEN2

Uncertain

0.50

D;D;D

FATHMM_MKL

Benign

0.054

LIST_S2

Uncertain

0.89

D;.;.

M_CAP

Benign

0.075

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.60

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.36

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.083

MutPred

0.34

Loss of ubiquitination at K344 (P = 0.0077);Loss of ubiquitination at K344 (P = 0.0077);Loss of ubiquitination at K344 (P = 0.0077);

MVP

0.73

MPC

0.95

ClinPred

0.032

GERP RS

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.58

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