rs742350

Variant names:

• chr1-171280905-C-T
• rs742350
• NM_001282693.2:c.747C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001282693.2(FMO1):​c.747C>T​(p.Thr249Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,384 control chromosomes in the GnomAD database, including 22,576 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 0.22 (5385 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17191 hom.)
• Consequence: FMO1 NM_001282693.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 21 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-1.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMO1	NM_001282693.2	c.747C>T	p.Thr249Thr	synonymous_variant	Exon 6 of 9	ENST00000617670.6	NP_001269622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMO1	ENST00000617670.6	c.747C>T	p.Thr249Thr	synonymous_variant	Exon 6 of 9	1	NM_001282693.2	ENSP00000481732.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33327 AN: 151964 Hom.: 5383 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.146 AC: 36603 AN: 251304 AF XY: 0.145

Gnomad AFR exome AF: 0.465

Gnomad AMR exome AF: 0.0762

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.0206

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.141 AC: 206730 AN: 1461302 Hom.: 17191 Cov.: 32 AF XY: 0.142 AC XY: 103265 AN XY: 726976

African (AFR) AF: 0.464 AC: 15532 AN: 33454

American (AMR) AF: 0.0821 AC: 3669 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3414 AN: 26124

East Asian (EAS) AF: 0.0182 AC: 722 AN: 39696

South Asian (SAS) AF: 0.175 AC: 15116 AN: 86242

European-Finnish (FIN) AF: 0.124 AC: 6606 AN: 53412

Middle Eastern (MID) AF: 0.168 AC: 969 AN: 5768

European-Non Finnish (NFE) AF: 0.136 AC: 151706 AN: 1111534

Other (OTH) AF: 0.149 AC: 8996 AN: 60376

GnomAD4 genome AF: 0.219 AC: 33340 AN: 152082 Hom.: 5385 Cov.: 32 AF XY: 0.215 AC XY: 15981 AN XY: 74368

African (AFR) AF: 0.456 AC: 18873 AN: 41420

American (AMR) AF: 0.117 AC: 1788 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3472

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5174

South Asian (SAS) AF: 0.187 AC: 900 AN: 4822

European-Finnish (FIN) AF: 0.126 AC: 1331 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9337 AN: 67992

Other (OTH) AF: 0.190 AC: 402 AN: 2112

Alfa AF: 0.166 Hom.: 8768

Bravo AF: 0.226

Asia WGS AF: 0.131 AC: 456 AN: 3478

EpiCase AF: 0.136

EpiControl AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-1.5
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: rs742350; hg19: chr1-171250044; COSMIC: COSV61445056; COSMIC: COSV61445056;