NM_001002294.3(FMO3):c.209C>T (p.Pro70Leu) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 7, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003562309.1

Allele description

NM_001002294.3(FMO3):c.209C>T (p.Pro70Leu)

Gene:

FMO3:flavin containing dimethylaniline monoxygenase 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q24.3

Genomic location:

Preferred name:

NM_001002294.3(FMO3):c.209C>T (p.Pro70Leu)

HGVS:

NC_000001.11:g.171103861C>T
NG_012690.1:g.17985C>T
NG_012690.2:g.17958C>T
NM_001002294.3:c.209C>TMANE SELECT
NM_001319173.2:c.149C>T
NM_001319174.2:c.133-3814C>T
NM_006894.6:c.209C>T
NP_001002294.1:p.Pro70Leu
NP_001306102.1:p.Pro50Leu
NP_008825.4:p.Pro70Leu
NP_008825.4:p.Pro70Leu
NC_000001.10:g.171073002C>T
NM_006894.4:c.209C>T

Protein change:

P50L

Molecular consequence:

NM_001319174.2:c.133-3814C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001002294.3:c.209C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001319173.2:c.149C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006894.6:c.209C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004293813	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22819296, 24028545, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293813

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 7, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Variants in the flavin-containing monooxygenase 3 (FMO3) gene responsible for trimethylaminuria in a Japanese population.

Shimizu M, Kobayashi Y, Hayashi S, Aoki Y, Yamazaki H.

Mol Genet Metab. 2012 Nov;107(3):330-4. doi: 10.1016/j.ymgme.2012.06.014. Epub 2012 Jul 1.

PubMed [citation]

PMID:: 22819296

Relationships between flavin-containing mono-oxygenase 3 (FMO3) genotype and trimethylaminuria phenotype in a Japanese population.

Shimizu M, Allerston CK, Shephard EA, Yamazaki H, Phillips IR.

Br J Clin Pharmacol. 2014 May;77(5):839-51. doi: 10.1111/bcp.12240.

PubMed [citation]

PMID:: 24028545
PMCID:: PMC4004404

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004293813.1

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

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects FMO3 function (PMID: 22819296). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FMO3 protein function. This missense change has been observed in individual(s) with trimethylaminuria (PMID: 22819296, 24028545). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 70 of the FMO3 protein (p.Pro70Leu).

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

Last Updated: Feb 20, 2024

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