Variant X-43838972-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000898.5(MAOB):c.175T>G(p.Ser59Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 1,199,097 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000063 ( 0 hom. 24 hem. )

Consequence

MAOB
NM_000898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18949515).

BS2

High Hemizygotes in GnomAdExome4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOB	NM_000898.5 linkuse as main transcript	c.175T>G	p.Ser59Ala	missense_variant	3/15	ENST00000378069.5	NP_000889.3
MAOB	XM_017029524.3 linkuse as main transcript	c.127T>G	p.Ser43Ala	missense_variant	3/15		XP_016885013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5 linkuse as main transcript	c.175T>G	p.Ser59Ala	missense_variant	3/15	1	NM_000898.5	ENSP00000367309	P1	P27338-1
MAOB	ENST00000487544.1 linkuse as main transcript	n.501T>G		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33710

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

175822

Hom.:

AF XY:

0.0000329

AC XY:

AN XY:

60766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000388

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000503

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000625

AC:

AN:

1087569

Hom.:

Cov.:

AF XY:

0.0000678

AC XY:

AN XY:

353899

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000777

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33710

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000753

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.175T>G (p.S59A) alteration is located in exon 3 (coding exon 3) of the MAOB gene. This alteration results from a T to G substitution at nucleotide position 175, causing the serine (S) at amino acid position 59 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.8

DANN

Benign

0.21

DEOGEN2

Uncertain

0.59

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.52

M_CAP

Benign

0.049

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.63

MutationAssessor

Benign

-1.6

MutationTaster

Benign

0.58

N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

1.5

REVEL

Benign

0.26

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.16

MVP

0.56

MPC

0.40

ClinPred

0.025

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.44

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over