1-171116174-AT-ATT

Position:

• chr1-171116174-AT-ATT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001002294.3(FMO3):​c.1184-32dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.31 (7969 hom., cov: 0)
  • Exomes 𝑓: 0.26 (43621 hom.)
• Consequence: FMO3 NM_001002294.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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]

ENSG00000231424 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-171116174-A-AT is Benign according to our data. Variant chr1-171116174-A-AT is described in ClinVar as [Benign]. Clinvar id is 260065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMO3	NM_001002294.3	c.1184-32dupT		intron_variant		ENST00000367755.9	NP_001002294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMO3	ENST00000367755.9	c.1184-32dupT		intron_variant		1	NM_001002294.3	ENSP00000356729.4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47498 AN: 151938 Hom.: 7951 Cov.: 0

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.287 AC: 71911 AN: 250132 Hom.: 11069 AF XY: 0.275 AC XY: 37152 AN XY: 135214

Gnomad AFR exome AF: 0.441

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.367

Gnomad SAS exome AF: 0.237

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.261 AC: 317162 AN: 1214582 Hom.: 43621 Cov.: 18 AF XY: 0.258 AC XY: 159417 AN XY: 617024

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.313 AC: 47567 AN: 152056 Hom.: 7969 Cov.: 0 AF XY: 0.314 AC XY: 23315 AN XY: 74332

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.267

Alfa AF: 0.259 Hom.: 1189

Bravo AF: 0.322

Asia WGS AF: 0.329 AC: 1140 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397820586; hg19: chr1-171085314;