rs766383334
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_001002294.3(FMO3):c.1479G>A(p.Ser493=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,954 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000085 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 1 hom. )
Consequence
FMO3
NM_001002294.3 synonymous
NM_001002294.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.513
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 -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 1-171117322-G-A is Benign according to our data. Variant chr1-171117322-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-171117322-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.513 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FMO3 | NM_001002294.3 | c.1479G>A | p.Ser493= | synonymous_variant | 9/9 | ENST00000367755.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FMO3 | ENST00000367755.9 | c.1479G>A | p.Ser493= | synonymous_variant | 9/9 | 1 | NM_001002294.3 | P1 | |
ENST00000669750.1 | n.533+50782C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152204Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000112 AC: 28AN: 250982Hom.: 2 AF XY: 0.000147 AC XY: 20AN XY: 135612
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GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461632Hom.: 1 Cov.: 32 AF XY: 0.0000811 AC XY: 59AN XY: 727086
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GnomAD4 genome AF: 0.0000853 AC: 13AN: 152322Hom.: 1 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74492
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | FMO3: BP4, BP7, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at