rs2066537
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001002294.3(FMO3):c.321+31C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000831 in 1,498,540 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0039 ( 7 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 6 hom. )
Consequence
FMO3
NM_001002294.3 intron
NM_001002294.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.500
Genes affected
FMO3 (HGNC:3771): (flavin containing dimethylaniline monoxygenase 3) Flavin-containing monooxygenases (FMO) are an important class of drug-metabolizing enzymes that catalyze the NADPH-dependent oxygenation of various nitrogen-,sulfur-, and phosphorous-containing xenobiotics such as therapeutic drugs, dietary compounds, pesticides, and other foreign compounds. The human FMO gene family is composed of 5 genes and multiple pseudogenes. FMO members have distinct developmental- and tissue-specific expression patterns. The expression of this FMO3 gene, the major FMO expressed in adult liver, can vary up to 20-fold between individuals. This inter-individual variation in FMO3 expression levels is likely to have significant effects on the rate at which xenobiotics are metabolised and, therefore, is of considerable interest to the pharmaceutical industry. This transmembrane protein localizes to the endoplasmic reticulum of many tissues. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. Mutations in this gene cause the disorder trimethylaminuria (TMAu) which is characterized by the accumulation and excretion of unmetabolized trimethylamine and a distinctive body odor. In healthy individuals, trimethylamine is primarily converted to the non odorous trimethylamine N-oxide.[provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 1-171104004-C-A is Benign according to our data. Variant chr1-171104004-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 260070.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FMO3 | NM_001002294.3 | c.321+31C>A | intron_variant | ENST00000367755.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FMO3 | ENST00000367755.9 | c.321+31C>A | intron_variant | 1 | NM_001002294.3 | P1 | |||
ENST00000669750.1 | n.533+64100G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00392 AC: 597AN: 152158Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.000948 AC: 234AN: 246724Hom.: 4 AF XY: 0.000839 AC XY: 112AN XY: 133494
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GnomAD4 exome AF: 0.000480 AC: 646AN: 1346264Hom.: 6 Cov.: 20 AF XY: 0.000445 AC XY: 301AN XY: 676118
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GnomAD4 genome ? AF: 0.00394 AC: 600AN: 152276Hom.: 7 Cov.: 32 AF XY: 0.00375 AC XY: 279AN XY: 74450
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at