Genetic Variant NM_000898.5:c.1465G>A (chrX-43767564-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000898.5(MAOB):c.1465G>A(p.Val489Met) 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 1,208,546 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000025 ( 0 hom. 11 hem. )

Consequence

MAOB
NM_000898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Publications

1 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 -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 11 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.1465G>A	p.Val489Met	missense	Exon 15 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.1465G>A	p.Val489Met	missense	Exon 15 of 15	ENSP00000367309.4	P27338-1
MAOB	ENST00000890313.1		c.1570G>A	p.Val524Met	missense	Exon 16 of 16	ENSP00000560372.1
MAOB	ENST00000890309.1		c.1483G>A	p.Val495Met	missense	Exon 15 of 15	ENSP00000560368.1

Frequencies

GnomAD3 genomes

AF:

0.0000358

AC:

AN:

111644

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000383

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000110

AC:

AN:

182390

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.0000761

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1096902

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

362412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26376

American (AMR)

AF:

0.00

AC:

AN:

35180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19375

East Asian (EAS)

AF:

0.00

AC:

AN:

30168

South Asian (SAS)

AF:

0.0000370

AC:

AN:

54003

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3898

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

841372

Other (OTH)

AF:

0.0000652

AC:

AN:

46012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000358

AC:

AN:

111644

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33826

show subpopulations

African (AFR)

AF:

0.0000652

AC:

AN:

30670

American (AMR)

AF:

0.00

AC:

AN:

10519

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3538

South Asian (SAS)

AF:

0.000383

AC:

AN:

2614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53158

Other (OTH)

AF:

0.00

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00

Hom.:

Bravo

AF:

0.0000113

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

Uncertain

0.38

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.63

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.9

PhyloP100

3.5

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.19

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.40

MutPred

0.29

Loss of glycosylation at S488 (P = 0.1413)

MVP

0.54

MPC

1.3

ClinPred

0.60

GERP RS

5.7

Varity_R

0.87

gMVP

0.94

Mutation Taster

=91/9

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over