chr1-40983405-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001905.4(CTPS1):c.115A>G(p.Ile39Val) 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: 33)
Consequence
CTPS1
NM_001905.4 missense
NM_001905.4 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 7.17
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]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
CTPS1 | NM_001905.4 | c.115A>G | p.Ile39Val | missense_variant | 2/19 | ENST00000650070.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTPS1 | ENST00000650070.2 | c.115A>G | p.Ile39Val | missense_variant | 2/19 | NM_001905.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe combined immunodeficiency due to CTPS1 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with CTPS1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 39 of the CTPS1 protein (p.Ile39Val). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.;M;.;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;.;N
REVEL
Benign
Sift
Benign
D;.;.;.;.;.;D
Sift4G
Uncertain
T;.;.;.;.;.;T
Polyphen
D;D;.;D;.;.;D
Vest4
MutPred
Loss of catalytic residue at P41 (P = 0.0481);Loss of catalytic residue at P41 (P = 0.0481);Loss of catalytic residue at P41 (P = 0.0481);Loss of catalytic residue at P41 (P = 0.0481);Loss of catalytic residue at P41 (P = 0.0481);Loss of catalytic residue at P41 (P = 0.0481);Loss of catalytic residue at P41 (P = 0.0481);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.