NM_001905.4:c.501A>T

Variant names:

• chr1-40988656-A-T
• rs5030799
• NM_001905.4:c.501A>T

Variant summary

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

The NM_001905.4(CTPS1):​c.501A>T​(p.Gln167His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q167Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTPS1 NM_001905.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 10 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):

• combined immunodeficiency due to CTPS1 deficiency

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

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_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.501A>T	p.Gln167His	missense	Exon 5 of 19	NP_001896.2	P17812-1
	CTPS1	NM_001301237.2		c.33A>T	p.Gln11His	missense	Exon 1 of 15	NP_001288166.1	B4E1E0
	CTPS1	NR_125440.2		n.648A>T		non_coding_transcript_exon	Exon 5 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTPS1	ENST00000650070.2	MANE Select	c.501A>T	p.Gln167His	missense	Exon 5 of 19	ENSP00000497602.1	P17812-1
	CTPS1	ENST00000372616.1	TSL:2	c.501A>T	p.Gln167His	missense	Exon 4 of 18	ENSP00000361699.1	P17812-1
	CTPS1	ENST00000470271.6	TSL:3	c.501A>T	p.Gln167His	missense	Exon 5 of 19	ENSP00000497901.2	P17812-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.15
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.74
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.47
Sift	Benign	0.035	D
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.70
MutPred		0.50		Loss of MoRF binding (P = 0.141)
MVP		0.86
MPC		1.4
ClinPred		0.99	D
GERP RS		-0.52
PromoterAI		-0.0083	Neutral
Varity_R		0.74
gMVP		0.90
Mutation Taster		=23/77	disease causing

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: rs5030799; hg19: chr1-41454328;