Variant 1-171199358-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 ENST00000209929.10(FMO2):c.497T>C(p.Phe166Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00544 in 1,608,106 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 26 hom. )

Consequence

FMO2
ENST00000209929.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.01

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:

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=0.025721163).

BP6

Variant 1-171199358-T-C is Benign according to our data. Variant chr1-171199358-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 774280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FMO2	NM_001460.5 linkuse as main transcript	c.497T>C	p.Phe166Ser	missense_variant	5/9	ENST00000209929.10	NP_001451.2
LOC124900413	XR_007066731.1 linkuse as main transcript	n.366-2420A>G		intron_variant, non_coding_transcript_variant
LOC105371611	XR_922278.4 linkuse as main transcript	n.515-31170A>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.497T>C	p.Phe166Ser	missense_variant	5/9	1	NM_001460.5	ENSP00000209929	P1
	ENST00000445290.1 linkuse as main transcript	n.296A>G		non_coding_transcript_exon_variant	2/2	2
	ENST00000669750.1 linkuse as main transcript	n.449-31170A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

624

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00688

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00644

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00396

AC:

972

AN:

245418

Hom.:

AF XY:

0.00384

AC XY:

509

AN XY:

132490

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00599

Gnomad ASJ exome

AF:

0.00185

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00116

Gnomad FIN exome

AF:

0.000234

Gnomad NFE exome

AF:

0.00597

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00558

AC:

8122

AN:

1455812

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

3938

AN XY:

723930

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00544

Gnomad4 ASJ exome

AF:

0.00159

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000908

Gnomad4 FIN exome

AF:

0.000733

Gnomad4 NFE exome

AF:

0.00661

Gnomad4 OTH exome

AF:

0.00550

GnomAD4 genome

AF:

0.00410

AC:

624

AN:

152294

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00687

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00644

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00571

Hom.:

Bravo

AF:

0.00478

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00361

AC:

438

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.026

MetaSVM

Uncertain

0.41

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-7.6

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Vest4

0.70

MVP

0.95

ClinPred

0.13

GERP RS

6.2

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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