Genetic Variant NM_000898.5:c.1514C>T (chrX-43767515-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000898.5(MAOB):c.1514C>T(p.Thr505Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,208,786 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 68 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T505A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00014 ( 0 hom. 64 hem. )

Consequence

MAOB
NM_000898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022457004).

BS2

High Hemizygotes in GnomAd4 at 4 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.1514C>T	p.Thr505Met	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.1514C>T	p.Thr505Met	missense	Exon 15 of 15	ENSP00000367309.4	P27338-1
MAOB	ENST00000890313.1		c.1619C>T	p.Thr540Met	missense	Exon 16 of 16	ENSP00000560372.1
MAOB	ENST00000890309.1		c.1532C>T	p.Thr511Met	missense	Exon 15 of 15	ENSP00000560368.1

Frequencies

GnomAD3 genomes

AF:

0.000188

AC:

AN:

111626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000953

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000381

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000245

Gnomad OTH

AF:

0.000664

GnomAD2 exomes

AF:

0.000115

AC:

AN:

182657

AF XY:

0.000164

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:

0.000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000144

AC:

158

AN:

1097103

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

362661

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26383

American (AMR)

AF:

0.00

AC:

AN:

35183

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19372

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30169

South Asian (SAS)

AF:

0.000629

AC:

AN:

54033

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40513

Middle Eastern (MID)

AF:

0.000781

AC:

AN:

3840

European-Non Finnish (NFE)

AF:

0.000132

AC:

111

AN:

841578

Other (OTH)

AF:

0.0000869

AC:

AN:

46032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.000188

AC:

AN:

111683

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33897

show subpopulations

African (AFR)

AF:

0.000163

AC:

AN:

30733

American (AMR)

AF:

0.0000952

AC:

AN:

10509

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3533

South Asian (SAS)

AF:

0.000382

AC:

AN:

2617

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000245

AC:

AN:

53155

Other (OTH)

AF:

0.000656

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000151

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

0.082

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.39

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.67

M_CAP

Benign

0.0042

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

2.4

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

REVEL

Benign

0.058

Sift

Benign

0.053

Sift4G

Uncertain

0.046

Polyphen

0.048

Vest4

0.027

MVP

0.20

MPC

0.50

ClinPred

0.028

GERP RS

0.52

Varity_R

0.031

gMVP

0.60

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over