rs1736561

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001002294.3(FMO3):​c.-7+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,722 control chromosomes in the GnomAD database, including 29,308 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 29308 hom., cov: 30)
Exomes 𝑓: 0.61 ( 10 hom. )
Failed GnomAD Quality Control

Consequence

FMO3
NM_001002294.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.836
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FMO3NM_001002294.3 linkuse as main transcriptc.-7+86G>A intron_variant ENST00000367755.9 NP_001002294.1 P31513A0A024R8Z4Q53FW5
FMO3NM_006894.6 linkuse as main transcriptc.-7+103G>A intron_variant NP_008825.4 P31513A0A024R8Z4Q53FW5
FMO3NM_001319173.2 linkuse as main transcriptc.-194+103G>A intron_variant NP_001306102.1 P31513B7Z543Q53FW5
FMO3NM_001319174.2 linkuse as main transcriptc.-7+86G>A intron_variant NP_001306103.1 P31513Q53FW5B7Z3M2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FMO3ENST00000367755.9 linkuse as main transcriptc.-7+86G>A intron_variant 1 NM_001002294.3 ENSP00000356729.4 P31513
FMO3ENST00000479749.1 linkuse as main transcriptc.-7+86G>A intron_variant 5 ENSP00000477451.1 V9GZ60

Frequencies

GnomAD3 genomes
AF:
0.614
AC:
93062
AN:
151604
Hom.:
29250
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.769
Gnomad AMI
AF:
0.397
Gnomad AMR
AF:
0.615
Gnomad ASJ
AF:
0.517
Gnomad EAS
AF:
0.596
Gnomad SAS
AF:
0.598
Gnomad FIN
AF:
0.522
Gnomad MID
AF:
0.500
Gnomad NFE
AF:
0.546
Gnomad OTH
AF:
0.573
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.606
AC:
40
AN:
66
Hom.:
10
AF XY:
0.620
AC XY:
31
AN XY:
50
show subpopulations
Gnomad4 NFE exome
AF:
0.606
GnomAD4 genome
AF:
0.614
AC:
93181
AN:
151722
Hom.:
29308
Cov.:
30
AF XY:
0.613
AC XY:
45474
AN XY:
74152
show subpopulations
Gnomad4 AFR
AF:
0.769
Gnomad4 AMR
AF:
0.616
Gnomad4 ASJ
AF:
0.517
Gnomad4 EAS
AF:
0.596
Gnomad4 SAS
AF:
0.597
Gnomad4 FIN
AF:
0.522
Gnomad4 NFE
AF:
0.546
Gnomad4 OTH
AF:
0.573
Alfa
AF:
0.581
Hom.:
3119
Bravo
AF:
0.626
Asia WGS
AF:
0.585
AC:
2035
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.64
DANN
Benign
0.69

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1736561; hg19: chr1-171060208; API