1-171334697-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002022.3(FMO4):c.1114G>A(p.Gly372Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,609,836 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 14 hom. )

Consequence

FMO4
NM_002022.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.429

Variant links:

Genes affected

FMO4 (HGNC:3772): (flavin containing dimethylaniline monoxygenase 4) Metabolic N-oxidation of diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man. This results in a small subpopulation with reduced TMA N-oxidation capacity and causes fish odor syndrome (Trimethylaminuria). Three forms of the enzyme 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. [provided by RefSeq, Jan 2015]

FMO4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004075408).

BP6

Variant 1-171334697-G-A is Benign according to our data. Variant chr1-171334697-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 787650.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO4	NM_002022.3 linkuse as main transcript	c.1114G>A	p.Gly372Ser	missense_variant	8/10	ENST00000367749.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FMO4	ENST00000367749.4 linkuse as main transcript	c.1114G>A	p.Gly372Ser	missense_variant	8/10	1	NM_002022.3	P1
FMO4	ENST00000480136.1 linkuse as main transcript	n.172G>A		non_coding_transcript_exon_variant	1/4	3
FMO4	ENST00000475780.5 linkuse as main transcript	n.652-2659G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

413

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00498

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00245

AC:

599

AN:

244656

Hom.:

AF XY:

0.00244

AC XY:

323

AN XY:

132478

show subpopulations

Gnomad AFR exome

AF:

0.000990

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000706

Gnomad FIN exome

AF:

0.000839

Gnomad NFE exome

AF:

0.00454

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.00450

AC:

6557

AN:

1457696

Hom.:

Cov.:

AF XY:

0.00437

AC XY:

3170

AN XY:

725176

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000843

Gnomad4 FIN exome

AF:

0.000881

Gnomad4 NFE exome

AF:

0.00552

Gnomad4 OTH exome

AF:

0.00349

GnomAD4 genome

AF:

0.00271

AC:

413

AN:

152140

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.00498

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00252

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00241

AC:

293

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00469

EpiControl

AF:

0.00427

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

Cadd

Benign

0.086

Dann

Benign

0.70

DEOGEN2

Benign

0.0098

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.17

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.050

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

1.4

REVEL

Benign

0.082

Sift

Benign

0.13

Sift4G

Benign

0.083

Polyphen

0.0070

Vest4

0.036

MVP

0.36

MPC

0.080

ClinPred

0.019

GERP RS

-11

Varity_R

0.034

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over