Genetic Variant MAOB:p.Glu366Asp (chrX-43778721-T-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000898.5(MAOB):c.1098A>C(p.Glu366Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,089,978 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000026 ( 0 hom. 8 hem. )

Consequence

MAOB
NM_000898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.313

Publications

0 publications found

Variant links:

Genes affected

MAOB (HGNC:6834): (monoamine oxidase B) The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is a enzyme located in the mitochondrial outer membrane. It catalyzes the oxidative deamination of biogenic and xenobiotic amines and plays an important role in the metabolism of neuroactive and vasoactive amines in the central nervous sysytem and peripheral tissues. This protein preferentially degrades benzylamine and phenylethylamine. [provided by RefSeq, Jul 2008]

MAOB links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20855835).

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000898.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOB	NM_000898.5	MANE Select	c.1098A>C	p.Glu366Asp	missense	Exon 11 of 15	NP_000889.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAOB	ENST00000378069.5	TSL:1 MANE Select	c.1098A>C	p.Glu366Asp	missense	Exon 11 of 15	ENSP00000367309.4	P27338-1
MAOB	ENST00000890313.1		c.1203A>C	p.Glu401Asp	missense	Exon 12 of 16	ENSP00000560372.1
MAOB	ENST00000890309.1		c.1098A>C	p.Glu366Asp	missense	Exon 11 of 15	ENSP00000560368.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000112

AC:

AN:

177916

AF XY:

0.0000159

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000257

AC:

AN:

1089978

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

355814

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26152

American (AMR)

AF:

0.00

AC:

AN:

34848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19244

East Asian (EAS)

AF:

0.00

AC:

AN:

29993

South Asian (SAS)

AF:

0.00

AC:

AN:

53246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4086

European-Non Finnish (NFE)

AF:

0.0000323

AC:

AN:

836169

Other (OTH)

AF:

0.0000218

AC:

AN:

45788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

ClinVar submissions as Germline

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

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Pathogenic

0.83

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.85

M_CAP

Benign

0.0045

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

-0.31

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.081

Sift

Benign

0.12

Sift4G

Benign

0.32

Polyphen

0.0010

Vest4

0.090

MutPred

0.46

Gain of MoRF binding (P = 0.122)

MVP

0.46

MPC

0.44

ClinPred

0.16

GERP RS

-0.24

Varity_R

0.73

gMVP

0.78

Mutation Taster

=96/4

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