NM_006894.5(FMO3):c.913G>T (p.Glu305Ter) AND Trimethylaminuria

Clinical significance:Pathogenic (Last evaluated: Jun 14, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000017697.30

Allele description

NM_006894.5(FMO3):c.913G>T (p.Glu305Ter)

Gene:
FMO3:flavin containing monooxygenase 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q24.3
Genomic location:
Preferred name:
NM_006894.5(FMO3):c.913G>T (p.Glu305Ter)
HGVS:
  • NC_000001.11:g.171114092G>T
  • NG_012690.1:g.28215G>T
  • NM_001002294.2:c.913G>T
  • NM_006894.5:c.913G>T
  • NP_001002294.1:p.Glu305Ter
  • NP_008825.4:p.Glu305Ter
  • NC_000001.10:g.171083232G>T
  • NM_006894.4:c.913G>T
Protein change:
E305*; GLU305TER
Links:
OMIM: 136132.0001; dbSNP: rs61753344
GMAF:
0.0002(T), 61753344
NCBI 1000 Genomes Browser:
rs61753344
Allele Frequency:
0.00031(T), GO-ESP
Molecular consequence:
  • NM_001002294.2:c.913G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Trimethylaminuria (TMAU)
Synonyms:
FISH-ODOR SYNDROME
Identifiers:
MedGen: C0342739; OMIM: 602079

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000037974OMIMno assertion criteria providedPathogenic
(Oct 21, 1976)
germlineliterature only

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

Akerman, B. R., Chow, L., Forrest, S., Youil, R., Cashman, J., Treacy, E. P. Mutations in the flavin-containing monoxygenase (sic) form 3 (FMO3) gene cause trimethylaminuria, fish odour syndrome. (Abstract) Am. J. Hum. Genet. 61 (suppl.): A53-only, 1997.,

SCV000041188GeneReviewsno assertion criteria providedpathologic
(Apr 19, 2011)
not providedcuration

SCV000351251Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Pathogenic
(Jun 14, 2016)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

ICSL_Variant_Classification_20161018.pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot providednot providednot providedliterature only
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Trimethylaminuria: diet does not always control the fishy odor.

Danks DM, Hammond J, Schlesinger P, Faull K, Burke D, Halpern B.

N Engl J Med. 1976 Oct 21;295(17):962. No abstract available.

PubMed [citation]
PMID:
987532

Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication.

Treacy EP, Akerman BR, Chow LM, Youil R, Bibeau C, Lin J, Bruce AG, Knight M, Danks DM, Cashman JR, Forrest SM.

Hum Mol Genet. 1998 May;7(5):839-45.

PubMed [citation]
PMID:
9536088
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000037974.3

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

Description

Akerman et al. (1997) identified a glu305-to-ter (E305X) mutation in the FMO3 gene in 6 mutant chromosomes from Australian probands of British origin with trimethylaminuria (TMAU; 602079). The mutation was homozygous in 1 and heterozygous in 4 individuals. The E305X homozygote had, in addition to trimethylaminuria, tachycardia and severe hypertension after eating cheese (which contains tyramine) and after using nasal epinephrine in the treatment of an epistaxis (Danks et al., 1976). The FMO3 enzyme metabolizes tyramine. Mutant FMO3 cDNA for this mutation demonstrated loss of substrate activity for TMA and tyramine when expressed in E. coli.

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

From GeneReviews, SCV000041188.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Converted during submission to Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000351251.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.913G>T (p.Glu305Ter) is a stop-gained variant and is one of the most common variants associated with trimethylaminuria. The p.Glu305Ter has been reported in two studies in a total of six patients including five in a compound heterozygous state with a second missense variant and one in a homozygous state (Treacy et al. 1998; Motika et al. 2009). The p.Glu305Ter variant was absent from 40 control chromosomes and is reported at a frequency of 0.00128 in the European American population of the Exome Sequencing Project. Functional studies in E.coli showed undetectable N-oxygenated product generated by the p.Glu305Ter variant (Treacy et al. 1998). Based on the collective evidence and the potential impact of stop-gained variants, the p.Glu305Ter variant is classified as pathogenic for trimethylaminuria.

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

Last Updated: Sep 14, 2017

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