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NM_001953.5(TYMP):c.929-1G>A AND Mitochondrial DNA depletion syndrome 1

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Feb 27, 2024
Review status:
criteria provided, conflicting classifications
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:
RCV000779376.5

Allele description [Variation Report for NM_001953.5(TYMP):c.929-1G>A]

NM_001953.5(TYMP):c.929-1G>A

Genes:
LOC130067862:ATAC-STARR-seq lymphoblastoid silent region 13986 [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.929-1G>A
HGVS:
  • NC_000022.11:g.50526477C>T
  • NG_011860.1:g.8609G>A
  • NG_016235.1:g.4963G>A
  • NG_021419.1:g.23262C>T
  • NM_001113755.3:c.929-1G>A
  • NM_001113756.3:c.929-1G>A
  • NM_001257988.1:c.929-1G>A
  • NM_001257989.1:c.929-1G>A
  • NM_001953.5:c.929-1G>AMANE SELECT
  • LRG_727t1:c.929-1G>A
  • LRG_727t2:c.929-1G>A
  • LRG_727:g.8609G>A
  • NC_000022.10:g.50964906C>T
  • NM_001953.4:c.929-1G>A
Links:
dbSNP: rs1180285291
NCBI 1000 Genomes Browser:
rs1180285291
Molecular consequence:
  • NM_001113755.3:c.929-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001113756.3:c.929-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001257988.1:c.929-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001257989.1:c.929-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001953.5:c.929-1G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000915978Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)		Uncertain significance
(Apr 28, 2017) 		germlineclinical testing

Citation Link,

SCV005054544Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 27, 2024) 		unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000915978.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The TYMP c.929-1G>A variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Due to the potential impact of splice acceptor variants and the lack of clarifying evidence, this variant is classified as a variant of uncertain significance but suspicious for pathogenicity for mitochondrial neurogastrointestinal encephalopathy disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV005054544.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024