U.S. flag

An official website of the United States government

NM_000367.5(TPMT):c.626-1G>A AND Thiopurine S-methyltransferase deficiency

Germline classification:
drug response (1 submission)
Last evaluated:
May 15, 2019
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000013560.20

Allele description [Variation Report for NM_000367.5(TPMT):c.626-1G>A]

NM_000367.5(TPMT):c.626-1G>A

Gene:
TPMT:thiopurine S-methyltransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p22.3
Genomic location:
Preferred name:
NM_000367.5(TPMT):c.626-1G>A
HGVS:
  • NC_000006.12:g.18130781C>T
  • NG_012137.3:g.29363G>A
  • NM_000367.5:c.626-1G>AMANE SELECT
  • NM_001346817.1:c.626-1G>A
  • NM_001346818.1:c.581-1G>A
  • LRG_874t1:c.626-1G>A
  • LRG_874:g.29363G>A
  • NC_000006.11:g.18131012C>T
  • NM_000367.3:c.626-1G>A
Note:
NCBI staff reviewed the sequence information reported in PubMed 9486974 Fig. 1 to determine the location of this allele on the current reference sequence.
Nucleotide change:
IVS9AS, G-A, -1
Links:
Genetic Testing Registry (GTR): GTR000613302; OMIM: 187680.0003; dbSNP: rs1800584
NCBI 1000 Genomes Browser:
rs1800584
Molecular consequence:
  • NM_000367.5:c.626-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001346817.1:c.626-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001346818.1:c.581-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Thiopurine S-methyltransferase deficiency
Synonyms:
Thiopurine S methyltranferase deficiency; TPMT deficiency; THIOPURINES, POOR METABOLISM OF, 1
Identifiers:
MONDO: MONDO:0012503; MedGen: C0342801; OMIM: 610460

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000033807OMIM
no assertion criteria provided
drug response
(May 15, 2019) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms.

Otterness D, Szumlanski C, Lennard L, Klemetsdal B, Aarbakke J, Park-Hah JO, Iven H, Schmiegelow K, Branum E, O'Brien J, Weinshilboum R.

Clin Pharmacol Ther. 1997 Jul;62(1):60-73.

PubMed [citation]
PMID:
9246020

Details of each submission

From OMIM, SCV000033807.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

This TPMT variant is referred to as TPMT*4A (Otterness et al., 1998).

In an individual with thiopurine S-methyltransferase deficiency (THPM1; 610460), Otterness et al. (1998) identified compound heterozygosity for 2 mutations in the TPMT gene: TPMT*3A (187680.0002) and a new variant allele, TPMT*4A, caused by a G-to-A transition that disrupted the acceptor splice junction at the final 3-prime nucleotide of intron 9. The new allele was found to cosegregate with reduced TPMT activity within an extended kindred. The mutation was found to lead to generation of at least 2 aberrant mRNA species. The first resulted from use of a novel splice site located 1 nucleotide 3-prime downstream from the original splice junction. This mRNA species contained a single nucleotide deletion and a frameshift in exon 10, the terminal exon of the gene. The second novel mRNA species resulted from activation of a cryptic splice site located within intron 9, leading to inclusion of 330 nucleotides of intron sequence. That sequence contained a premature translation termination codon. TPMT*4 was the first reported allele for low TPMT activity as a result of a mutation within an intron.

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

Last Updated: Oct 26, 2024