Variant 1-147201163-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001461.4(FMO5):c.1172A>G(p.Gln391Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,610,614 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 52 hom. )

Consequence

FMO5
NM_001461.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

FMO5 (HGNC:3773): (flavin containing dimethylaniline monoxygenase 5) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

FMO5 links:

CHD1L (HGNC:):

CHD1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007174343).

BP6

Variant 1-147201163-T-C is Benign according to our data. Variant chr1-147201163-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 781779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMO5	NM_001461.4 linkuse as main transcript	c.1172A>G	p.Gln391Arg	missense_variant	7/9	ENST00000254090.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMO5	ENST00000254090.9 linkuse as main transcript	c.1172A>G	p.Gln391Arg	missense_variant	7/9	1	NM_001461.4	P1	P49326-1

Frequencies

GnomAD3 genomes

AF:

0.00388

AC:

591

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00450

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00464

AC:

1156

AN:

249154

Hom.:

AF XY:

0.00487

AC XY:

656

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.0455

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00275

Gnomad FIN exome

AF:

0.000419

Gnomad NFE exome

AF:

0.00420

Gnomad OTH exome

AF:

0.00742

GnomAD4 exome

AF:

0.00475

AC:

6932

AN:

1458308

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

3489

AN XY:

725528

show subpopulations

Gnomad4 AFR exome

AF:

0.000662

Gnomad4 AMR exome

AF:

0.00285

Gnomad4 ASJ exome

AF:

0.0452

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00312

Gnomad4 FIN exome

AF:

0.000563

Gnomad4 NFE exome

AF:

0.00441

Gnomad4 OTH exome

AF:

0.00658

GnomAD4 genome

AF:

0.00388

AC:

591

AN:

152306

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00450

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00586

Hom.:

Bravo

AF:

0.00390

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00408

AC:

495

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00513

EpiControl

AF:

0.00539

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	FMO5: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.81

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.66

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0072

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.4

N;N;N

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

2.7

N;.;N

REVEL

Benign

0.088

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.096

MVP

0.081

MPC

0.030

ClinPred

0.0082

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.083

gMVP

0.66

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