NM_001282693.2:c.494C>T

Variant names:

• chr1-171278738-C-T
• rs201784982
• NM_001282693.2:c.494C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001282693.2(FMO1):​c.494C>T​(p.Ala165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,601,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: FMO1 NM_001282693.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.53
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12452981).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282693.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO1	NM_001282693.2	MANE Select	c.494C>T	p.Ala165Val	missense	Exon 5 of 9	NP_001269622.1	Q01740-1
	FMO1	NM_001282692.1		c.506C>T	p.Ala169Val	missense	Exon 4 of 8	NP_001269621.1	Q01740
	FMO1	NM_002021.3		c.494C>T	p.Ala165Val	missense	Exon 5 of 9	NP_002012.1	Q01740-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMO1	ENST00000617670.6	TSL:1 MANE Select	c.494C>T	p.Ala165Val	missense	Exon 5 of 9	ENSP00000481732.1	Q01740-1
	FMO1	ENST00000354841.4	TSL:1	c.494C>T	p.Ala165Val	missense	Exon 4 of 8	ENSP00000346901.4	Q01740-1
	FMO1	ENST00000367750.7	TSL:1	c.494C>T	p.Ala165Val	missense	Exon 5 of 9	ENSP00000356724.3	Q01740-1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152114 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000282 AC: 7 AN: 248522 AF XY: 0.0000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000591

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000207 AC: 30 AN: 1449374 Hom.: 0 Cov.: 28 AF XY: 0.0000263 AC XY: 19 AN XY: 721232

African (AFR) AF: 0.0000906 AC: 3 AN: 33126

American (AMR) AF: 0.0000226 AC: 1 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25754

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 84732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5724

European-Non Finnish (NFE) AF: 0.0000145 AC: 16 AN: 1103366

Other (OTH) AF: 0.0000669 AC: 4 AN: 59776

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74416

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.000262 AC: 4 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000534 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N
PhyloP100		-1.5
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.053
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.044	D
Polyphen		0.15	B
Vest4		0.22
MVP		0.39
MPC		0.12
ClinPred		0.089	T
GERP RS		-0.37
Varity_R		0.14
gMVP		0.24
Mutation Taster		=99/1	polymorphism

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: rs201784982; hg19: chr1-171247877; COSMIC: COSV61444855; COSMIC: COSV61444855;