NM_175859.3:c.1626G>C

Variant names:

• chrX-16609606-C-G
• rs151240507
• NM_175859.3:c.1626G>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_175859.3(CTPS2):​c.1626G>C​(p.Gly542Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,209,204 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 101 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G542G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., 47 hem., cov: 23)
  • Exomes 𝑓: 0.00018 (0 hom. 54 hem.)
• Consequence: CTPS2 NM_175859.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.64
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-16609606-C-G is Benign according to our data. Variant chrX-16609606-C-G is described in ClinVar as Benign. ClinVar VariationId is 721651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 47 gene

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.1626G>C	p.Gly542Gly	synonymous	Exon 17 of 19	NP_787055.1	Q9NRF8
	CTPS2	NM_001144002.2		c.1626G>C	p.Gly542Gly	synonymous	Exon 17 of 19	NP_001137474.1	Q9NRF8
	CTPS2	NM_019857.5		c.1626G>C	p.Gly542Gly	synonymous	Exon 17 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.1626G>C	p.Gly542Gly	synonymous	Exon 17 of 19	ENSP00000352222.4	Q9NRF8
	CTPS2	ENST00000380241.7	TSL:1	c.1626G>C	p.Gly542Gly	synonymous	Exon 17 of 19	ENSP00000369590.3	Q9NRF8
	CTPS2	ENST00000944988.1		c.1713G>C	p.Gly571Gly	synonymous	Exon 17 of 19	ENSP00000615047.1

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 164 AN: 111550 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000957

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000409 AC: 75 AN: 183356 AF XY: 0.000265

Gnomad AFR exome AF: 0.00479

Gnomad AMR exome AF: 0.000109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000733

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.000185 AC: 203 AN: 1097602 Hom.: 0 Cov.: 29 AF XY: 0.000149 AC XY: 54 AN XY: 362964

African (AFR) AF: 0.00584 AC: 154 AN: 26383

American (AMR) AF: 0.000142 AC: 5 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30196

South Asian (SAS) AF: 0.0000924 AC: 5 AN: 54103

European-Finnish (FIN) AF: 0.0000493 AC: 2 AN: 40531

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4128

European-Non Finnish (NFE) AF: 0.0000202 AC: 17 AN: 841608

Other (OTH) AF: 0.000391 AC: 18 AN: 46071

GnomAD4 genome AF: 0.00147 AC: 164 AN: 111602 Hom.: 0 Cov.: 23 AF XY: 0.00139 AC XY: 47 AN XY: 33802

African (AFR) AF: 0.00530 AC: 163 AN: 30734

American (AMR) AF: 0.0000956 AC: 1 AN: 10457

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3573

South Asian (SAS) AF: 0.00 AC: 0 AN: 2619

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5979

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53164

Other (OTH) AF: 0.00 AC: 0 AN: 1532

Alfa AF: 0.000477 Hom.: 1

Bravo AF: 0.00145

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.46
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs151240507; hg19: chrX-16627729;