Variant 1-171199406-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000209929.10(FMO2):c.545T>C(p.Phe182Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 1,611,428 control chromosomes in the GnomAD database, including 8,507 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1177 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7330 hom. )

Consequence

FMO2
ENST00000209929.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

FMO2 (HGNC:3770): (flavin containing dimethylaniline monoxygenase 2) This gene encodes a flavin-containing monooxygenase family member. It is an NADPH-dependent enzyme that catalyzes the N-oxidation of some primary alkylamines through an N-hydroxylamine intermediate. However, some human populations contain an allele (FMO2*2A) with a premature stop codon, resulting in a protein that is C-terminally-truncated, has no catalytic activity, and is likely degraded rapidly. This gene is found in a cluster with other related family members on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

FMO2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017034411).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FMO2	NM_001460.5 linkuse as main transcript	c.545T>C	p.Phe182Ser	missense_variant	5/9	ENST00000209929.10	NP_001451.2
LOC124900413	XR_007066731.1 linkuse as main transcript	n.366-2468A>G		intron_variant, non_coding_transcript_variant
LOC105371611	XR_922278.4 linkuse as main transcript	n.515-31218A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FMO2	ENST00000209929.10 linkuse as main transcript	c.545T>C	p.Phe182Ser	missense_variant	5/9	1	NM_001460.5	ENSP00000209929	P1
	ENST00000445290.1 linkuse as main transcript	n.248A>G		non_coding_transcript_exon_variant	2/2	2
	ENST00000669750.1 linkuse as main transcript	n.449-31218A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17797

AN:

151984

Hom.:

1176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.0443

Gnomad SAS

AF:

0.0916

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0965

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.104

AC:

25912

AN:

249292

Hom.:

1530

AF XY:

0.103

AC XY:

13815

AN XY:

134742

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.0458

Gnomad EAS exome

AF:

0.0446

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.0955

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.0963

AC:

140493

AN:

1459328

Hom.:

7330

Cov.:

AF XY:

0.0965

AC XY:

70088

AN XY:

725982

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.0468

Gnomad4 EAS exome

AF:

0.0345

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.0940

Gnomad4 OTH exome

AF:

0.0968

GnomAD4 genome

AF:

0.117

AC:

17803

AN:

152100

Hom.:

1177

Cov.:

AF XY:

0.117

AC XY:

8734

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.0442

Gnomad4 SAS

AF:

0.0913

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.0965

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0995

Hom.:

2074

Bravo

AF:

0.120

TwinsUK

AF:

0.0955

AC:

354

ALSPAC

AF:

0.0983

AC:

379

ESP6500AA

AF:

0.176

AC:

777

ESP6500EA

AF:

0.0971

AC:

835

ExAC

AF:

0.106

AC:

12856

Asia WGS

AF:

0.0650

AC:

228

AN:

3478

EpiCase

AF:

0.0913

EpiControl

AF:

0.0922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0017

MetaSVM

Uncertain

0.23

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-6.9

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.23

ClinPred

0.13

GERP RS

5.0

gMVP

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over