NM_001905.4(CTPS1):c.1692-1G>C AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 10, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000413591.5

Allele description [Variation Report for NM_001905.4(CTPS1):c.1692-1G>C]

NM_001905.4(CTPS1):c.1692-1G>C

Gene:

CTPS1:CTP synthase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_001905.4(CTPS1):c.1692-1G>C

HGVS:

NC_000001.11:g.41010160G>C
NG_034208.1:g.35862G>C
NM_001301237.2:c.1224-1G>C
NM_001905.4:c.1692-1G>CMANE SELECT
LRG_1229t1:c.1692-1G>C
LRG_1229:g.35862G>C
NC_000001.10:g.41475832G>C
NM_001905.2:c.1692-1G>C
NM_001905.3:c.1692-1G>C

Nucleotide change:

IVS17, G-C, -1 (rs145092287)

Links:

OMIM: 123860.0001; dbSNP: rs145092287

NCBI 1000 Genomes Browser:

rs145092287

Molecular consequence:

NM_001301237.2:c.1224-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001905.4:c.1692-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490997	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 10, 2024)	germline	clinical testing	Citation Link,
SCV002502201	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 8, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24870241, 27638562, 32161190, 25741868
SCV003839409	Genetic Services Laboratory, University of Chicago	no assertion criteria provided	Pathogenic (Sep 16, 2022)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490997

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 10, 2024)

germline

clinical testing

Citation Link,

SCV002502201

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 8, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV003839409

Genetic Services Laboratory, University of Chicago

no assertion criteria provided

Pathogenic
(Sep 16, 2022)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation.

Martin E, Palmic N, Sanquer S, Lenoir C, Hauck F, Mongellaz C, Fabrega S, Nitschké P, Esposti MD, Schwartzentruber J, Taylor N, Majewski J, Jabado N, Wynn RF, Picard C, Fischer A, Arkwright PD, Latour S.

Nature. 2014 Jun 12;510(7504):288-92. doi: 10.1038/nature13386. Epub 2014 May 28. Erratum in: Nature. 2014 Jul 17;511(7509):370.

PubMed [citation]

PMID:: 24870241
PMCID:: PMC6485470

CTP Synthase 1 Deficiency in Successfully Transplanted Siblings with Combined Immune Deficiency and Chronic Active EBV Infection.

Kucuk ZY, Zhang K, Filipovich L, Bleesing JJ.

J Clin Immunol. 2016 Nov;36(8):750-753. Epub 2016 Sep 14. No abstract available.

PubMed [citation]

PMID:: 27638562

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000490997.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24870241, 27638562, 34758253, 27543071, 31345272, 35983265, 32812031, 32161190)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From AiLife Diagnostics, AiLife Diagnostics, SCV002502201.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV003839409.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

DNA sequence analysis of the CTPS1 gene demonstrated a sequence change in the canonical splice acceptor site of intron 17, c.1692-1G>C. This sequence change is predicted to affect normal splicing of the CTPS1 gene and result in an abnormal/unstable protein. This sequence change has been previously described in the homozygous state in multiple individuals with CTPS1-related combined immunodeficiency (PMIDs: 24870241, 27638562, 32161190) and is reported to be a founder mutation in the northwest England population. Experimental studies have shown that this sequence change is responsible for reduced protein expression and may result in unstable protein lacking the last exon (PMIDs: 24870241, 32161190). This sequence change has been described in the gnomAD database with a frequency of 0.018% in the European subpopulation (dbSNP rs145092287). These collective evidences indicate that this sequence change is pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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