NM_175859.3:c.868G>T

Variant names:

• chrX-16689454-C-A
• rs1923514111
• NM_175859.3:c.868G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_175859.3(CTPS2):​c.868G>T​(p.Asp290Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CTPS2 NM_175859.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175859.3. 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
	CTPS2	NM_175859.3	MANE Select	c.868G>T	p.Asp290Tyr	missense	Exon 8 of 19	NP_787055.1	Q9NRF8
	CTPS2	NM_001144002.2		c.868G>T	p.Asp290Tyr	missense	Exon 8 of 19	NP_001137474.1	Q9NRF8
	CTPS2	NM_019857.5		c.868G>T	p.Asp290Tyr	missense	Exon 8 of 19	NP_062831.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTPS2	ENST00000359276.9	TSL:1 MANE Select	c.868G>T	p.Asp290Tyr	missense	Exon 8 of 19	ENSP00000352222.4	Q9NRF8
	CTPS2	ENST00000380241.7	TSL:1	c.868G>T	p.Asp290Tyr	missense	Exon 8 of 19	ENSP00000369590.3	Q9NRF8
	CTPS2	ENST00000944988.1		c.868G>T	p.Asp290Tyr	missense	Exon 8 of 19	ENSP00000615047.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.8
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.24
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.035	D
Polyphen		0.26	B
Vest4		0.52
MutPred		0.30		Gain of MoRF binding (P = 0.0572)
MVP		0.62
MPC		1.9
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.63
gMVP		0.91
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1923514111; hg19: chrX-16707577;