NM_001953.5(TYMP):c.215-1G>C AND Mitochondrial DNA depletion syndrome 1

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Mar 12, 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:: RCV000018142.31

Allele description [Variation Report for NM_001953.5(TYMP):c.215-1G>C]

NM_001953.5(TYMP):c.215-1G>C

Genes:

LOC130067864:ATAC-STARR-seq lymphoblastoid active region 19325 [Gene]
TYMP:thymidine phosphorylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_001953.5(TYMP):c.215-1G>C

HGVS:

NC_000022.11:g.50529339C>G
NG_011860.1:g.5747G>C
NG_016235.1:g.2101G>C
NM_001113755.3:c.215-1G>C
NM_001113756.3:c.215-1G>C
NM_001257988.1:c.215-1G>C
NM_001257989.1:c.215-1G>C
NM_001953.5:c.215-1G>CMANE SELECT
LRG_727t1:c.215-1G>C
LRG_727t2:c.215-1G>C
LRG_727:g.5747G>C
NC_000022.10:g.50967768C>G
NM_001953.3:c.215-1G>C
NM_001953.4:c.215-1G>C
NM_001953.4:c.215_417del
c.1-11G>C
c.215-1G>C

Note:

Single nucleotide change at exon 2 splice acceptor causes skipping of exon 2 in the product of gene TYMP.

Nucleotide change:

IVS1AS, G-C, -1

Links:

OMIM: 131222.0010; dbSNP: rs767245071

NCBI 1000 Genomes Browser:

rs767245071

Molecular consequence:

NM_001113755.3:c.215-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001113756.3:c.215-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001257988.1:c.215-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001257989.1:c.215-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001953.5:c.215-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Mitochondrial DNA depletion syndrome 1
Synonyms:: POLIP SYNDROME; POLYNEUROPATHY, OPHTHALMOPLEGIA, LEUKOENCEPHALOPATHY, AND INTESTINAL PSEUDOOBSTRUCTION; MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, TYMP-RELATED; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011283; MedGen: C4551995; Orphanet: 298; OMIM: 603041

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038421	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2004)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000264541	GeneReviews	no assertion criteria provided	Pathogenic (Jan 14, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000264542	GeneReviews	no assertion criteria provided	Pathogenic (Jan 14, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000799642	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Pathogenic (May 1, 2018)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14757860, 14720311, 20232099 Citation Link,
SCV004207504	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 12, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation.

Szigeti K, Wong LJ, Perng CL, Saifi GM, Eldin K, Adesina AM, Cass DL, Hirano M, Lupski JR, Scaglia F.

J Med Genet. 2004 Feb;41(2):125-9.

PubMed [citation]

PMID:: 14757860
PMCID:: PMC1735672

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a disease of two genomes.

Hirano M, Nishigaki Y, Martí R.

Neurologist. 2004 Jan;10(1):8-17. Review.

PubMed [citation]

PMID:: 14720311

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000038421.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with mitochondrial DNA depletion syndrome-1 (MTDPS1; 603041), manifest as classic mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) but without skeletal muscle involvement at the morphologic, enzymatic, or mtDNA level, Szigeti et al. (2004) identified a homozygous G-to-C transversion at the splice acceptor site of exon 2 of the ECGF1 gene. The mutation resulted in skipping of exon 2 and loss of function of the protein, which was confirmed by the markedly reduced enzyme activity measured in peripheral blood.

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

From GeneReviews, SCV000264541.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	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 GeneReviews, SCV000264542.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	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 Counsyl, SCV000799642.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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

From Baylor Genetics, SCV004207504.2

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

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

Last Updated: Sep 29, 2024

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