NM_001282693.2:c.-6-3134C>G

Variant names:

• chr1-171254948-C-G
• rs10798294
• NM_001282693.2:c.-6-3134C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282693.2(FMO1):​c.-6-3134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,104 control chromosomes in the GnomAD database, including 15,260 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 0.41 (15260 hom., cov: 32)
• Consequence: FMO1 NM_001282693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 2 publications found

Genes affected

FMO1 (HGNC:3769): (flavin containing dimethylaniline monoxygenase 1) 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMO1	NM_001282693.2	c.-6-3134C>G		intron_variant	Intron 1 of 8	ENST00000617670.6	NP_001269622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMO1	ENST00000617670.6	c.-6-3134C>G		intron_variant	Intron 1 of 8	1	NM_001282693.2	ENSP00000481732.1
FMO1	ENST00000367750.7	c.-6-3134C>G		intron_variant	Intron 1 of 8	1		ENSP00000356724.3
FMO1	ENST00000402921.6	c.-6-3134C>G		intron_variant	Intron 1 of 7	2		ENSP00000385543.2

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62094 AN: 151986 Hom.: 15243 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 62161 AN: 152104 Hom.: 15260 Cov.: 32 AF XY: 0.405 AC XY: 30126 AN XY: 74374

African (AFR) AF: 0.694 AC: 28792 AN: 41486

American (AMR) AF: 0.351 AC: 5368 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1240 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1240 AN: 5172

South Asian (SAS) AF: 0.458 AC: 2204 AN: 4812

European-Finnish (FIN) AF: 0.218 AC: 2309 AN: 10590

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19852 AN: 67976

Other (OTH) AF: 0.359 AC: 758 AN: 2114

Alfa AF: 0.212 Hom.: 512

Bravo AF: 0.426

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.83
DANN	Benign	0.37
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10798294; hg19: chr1-171224087;