dbSNP rs143909840: MAOB:p.Ala161Ser (chrX-43797262-C-A) – 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.481G>T(p.Ala161Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,176,334 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 0 hom. 41 hem. )

Consequence

MAOB
NM_000898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.22

Publications

2 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:

Genome browser will be placed here

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=0.1248686).

BS2

High Hemizygotes in GnomAd4 at 6 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.481G>T	p.Ala161Ser	missense	Exon 6 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.481G>T	p.Ala161Ser	missense	Exon 6 of 15	ENSP00000367309.4	P27338-1
MAOB	ENST00000890313.1		c.481G>T	p.Ala161Ser	missense	Exon 6 of 16	ENSP00000560372.1
MAOB	ENST00000890309.1		c.481G>T	p.Ala161Ser	missense	Exon 6 of 15	ENSP00000560368.1

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111839

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000377

Gnomad FIN

AF:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000301

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000178

AC:

AN:

162586

AF XY:

0.000119

show subpopulations

Gnomad AFR exome

AF:

0.0000806

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000130

Gnomad NFE exome

AF:

0.000348

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000113

AC:

120

AN:

1064442

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

335304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25576

American (AMR)

AF:

0.00

AC:

AN:

31618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18400

East Asian (EAS)

AF:

0.0000341

AC:

AN:

29317

South Asian (SAS)

AF:

0.000108

AC:

AN:

46250

European-Finnish (FIN)

AF:

0.0000751

AC:

AN:

39931

Middle Eastern (MID)

AF:

0.000499

AC:

AN:

4007

European-Non Finnish (NFE)

AF:

0.000125

AC:

103

AN:

824644

Other (OTH)

AF:

0.000134

AC:

AN:

44699

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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

AF:

0.000170

AC:

AN:

111892

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34084

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30805

American (AMR)

AF:

0.00

AC:

AN:

10561

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3559

South Asian (SAS)

AF:

0.000378

AC:

AN:

2647

European-Finnish (FIN)

AF:

0.000165

AC:

AN:

6077

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000301

AC:

AN:

53177

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000243

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000157

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.78

M_CAP

Benign

0.078

MetaRNN

Benign

0.12

MetaSVM

Uncertain

0.0093

MutationAssessor

Uncertain

2.8

PhyloP100

1.2

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.34

Sift

Benign

0.081

Sift4G

Benign

0.19

Polyphen

0.0050

Vest4

0.15

MVP

0.89

MPC

0.44

ClinPred

0.070

GERP RS

-0.20

Varity_R

0.22

gMVP

0.63

Mutation Taster

=92/8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over