chr1-40988656-A-T

Position:

• chr1-40988656-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTPS1	NM_001905.4	c.501A>T	p.Gln167His	missense_variant	5/19	ENST00000650070.2	NP_001896.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTPS1	ENST00000650070.2	c.501A>T	p.Gln167His	missense_variant	5/19		NM_001905.4	ENSP00000497602.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;.;D;.;D;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.97	.;.;D;.;D;D;D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.5	M;M;.;M;.;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.2	D;.;.;.;.;D;.
REVEL	Uncertain	0.47
Sift	Benign	0.035	D;.;.;.;.;D;.
Sift4G	Uncertain	0.054	T;.;.;.;.;T;.
Polyphen		1.0	D;D;.;D;.;D;.
Vest4		0.70
MutPred		0.50		Loss of MoRF binding (P = 0.141);Loss of MoRF binding (P = 0.141);Loss of MoRF binding (P = 0.141);Loss of MoRF binding (P = 0.141);Loss of MoRF binding (P = 0.141);Loss of MoRF binding (P = 0.141);.;
MVP		0.86
MPC		1.4
ClinPred		0.99	D
GERP RS		-0.52
Varity_R		0.74
gMVP		0.90

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

Other links and lift over

dbSNP: rs5030799; hg19: chr1-41454328;