Genetic Variant FMO2:p.Glu48Lys (chr1-171193344-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001460.5(FMO2):c.142G>A(p.Glu48Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,370 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FMO2
NM_001460.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42

Publications

1 publications found

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:

FMO1-AS1 (HGNC:40240):

FMO1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001460.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMO2	NM_001460.5	MANE Select	c.142G>A	p.Glu48Lys	missense	Exon 3 of 9	NP_001451.2	Q99518
FMO2	NM_001365900.2		c.-54G>A		5_prime_UTR	Exon 2 of 8	NP_001352829.1
FMO2	NM_001301347.2		c.-376G>A		5_prime_UTR	Exon 2 of 7	NP_001288276.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMO2	ENST00000209929.10	TSL:1 MANE Select	c.142G>A	p.Glu48Lys	missense	Exon 3 of 9	ENSP00000209929.8	Q99518
FMO2	ENST00000895514.1		c.142G>A	p.Glu48Lys	missense	Exon 3 of 9	ENSP00000565573.1
FMO2	ENST00000895513.1		c.139G>A	p.Glu47Lys	missense	Exon 3 of 9	ENSP00000565572.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000831

AC:

AN:

240652

AF XY:

0.00000770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446370

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32372

American (AMR)

AF:

0.00

AC:

AN:

41700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25824

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39508

South Asian (SAS)

AF:

0.00

AC:

AN:

82900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105352

Other (OTH)

AF:

0.00

AC:

AN:

59874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.65

PhyloP100

6.4

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.26

Sift

Benign

0.14

Sift4G

Benign

0.24

Vest4

0.37

MutPred

0.71

Gain of MoRF binding (P = 0.0064)

MVP

0.67

ClinPred

0.93

GERP RS

5.2

gMVP

0.59

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over