rs372743741

Variant names:

• chr1-40997401-C-A
• rs372743741
• NM_001905.4:c.880C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-40997401-C-A
• chr1-40997401-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001905.4(CTPS1):​c.880C>A​(p.Arg294Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R294H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTPS1 NM_001905.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 0 publications found

Genes affected

CTPS1 (HGNC:2519): (CTP synthase 1) This gene encodes an enzyme responsible for the catalytic conversion of UTP (uridine triphosphate) to CTP (cytidine triphospate). This reaction is an important step in the biosynthesis of phospholipids and nucleic acids. Activity of this proten is important in the immune system, and loss of function of this gene has been associated with immunodeficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CTPS1 Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to CTPS1 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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=0.20105967).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001905.4. 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
	CTPS1	NM_001905.4	MANE Select	c.880C>A	p.Arg294Ser	missense	Exon 9 of 19	NP_001896.2
	CTPS1	NM_001301237.2		c.412C>A	p.Arg138Ser	missense	Exon 5 of 15	NP_001288166.1
	CTPS1	NR_125440.2		n.1027C>A		non_coding_transcript_exon	Exon 9 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTPS1	ENST00000650070.2	MANE Select	c.880C>A	p.Arg294Ser	missense	Exon 9 of 19	ENSP00000497602.1
	CTPS1	ENST00000372616.1	TSL:2	c.880C>A	p.Arg294Ser	missense	Exon 8 of 18	ENSP00000361699.1
	CTPS1	ENST00000470271.6	TSL:3	c.880C>A	p.Arg294Ser	missense	Exon 9 of 19	ENSP00000497901.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	0.0049	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.0035
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.53	T
Sift4G	Benign	0.74	T
Polyphen		0.038	B
Vest4		0.71
MutPred		0.41		Loss of MoRF binding (P = 0.0357)
MVP		0.72
MPC		1.1
ClinPred		0.63	D
GERP RS		4.1
Varity_R		0.51
gMVP		0.81
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs372743741; hg19: chr1-41463073;