chr1-147201336-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001461.4(FMO5):c.999C>T(p.Ser333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,614,162 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 19 hom. )
Consequence
FMO5
NM_001461.4 synonymous
NM_001461.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.552
Genes affected
FMO5 (HGNC:3773): (flavin containing dimethylaniline monoxygenase 5) Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 1-147201336-G-A is Benign according to our data. Variant chr1-147201336-G-A is described in ClinVar as [Benign]. Clinvar id is 783294.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.552 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00513 (781/152286) while in subpopulation AFR AF= 0.0166 (692/41562). AF 95% confidence interval is 0.0156. There are 6 homozygotes in gnomad4. There are 394 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FMO5 | NM_001461.4 | c.999C>T | p.Ser333= | synonymous_variant | 7/9 | ENST00000254090.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FMO5 | ENST00000254090.9 | c.999C>T | p.Ser333= | synonymous_variant | 7/9 | 1 | NM_001461.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00513 AC: 780AN: 152168Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00269 AC: 675AN: 251258Hom.: 14 AF XY: 0.00271 AC XY: 368AN XY: 135810
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GnomAD4 exome AF: 0.00119 AC: 1733AN: 1461876Hom.: 19 Cov.: 32 AF XY: 0.00138 AC XY: 1003AN XY: 727238
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GnomAD4 genome AF: 0.00513 AC: 781AN: 152286Hom.: 6 Cov.: 32 AF XY: 0.00529 AC XY: 394AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at