Variant X-43767515-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 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

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 Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOB	NM_000898.5 linkuse as main transcript	c.1514C>T	p.Thr505Met	missense_variant	15/15	ENST00000378069.5	NP_000889.3
MAOB	XM_017029524.3 linkuse as main transcript	c.1466C>T	p.Thr489Met	missense_variant	15/15		XP_016885013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5 linkuse as main transcript	c.1514C>T	p.Thr505Met	missense_variant	15/15	1	NM_000898.5	ENSP00000367309	P1	P27338-1

Frequencies

GnomAD3 genomes

AF:

0.000188

AC:

AN:

111626

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33830

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

GnomAD3 exomes

AF:

0.000115

AC:

AN:

182657

Hom.:

AF XY:

0.000164

AC XY:

AN XY:

67247

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 SAS exome

AF:

0.000370

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

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000629

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.000188

AC:

AN:

111683

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33897

show subpopulations

Gnomad4 AFR

AF:

0.000163

Gnomad4 AMR

AF:

0.0000952

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000382

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000245

Gnomad4 OTH

AF:

0.000656

Alfa

AF:

0.000163

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

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

Apr 24, 2024

The c.1514C>T (p.T505M) alteration is located in exon 15 (coding exon 15) of the MAOB gene. This alteration results from a C to T substitution at nucleotide position 1514, causing the threonine (T) at amino acid position 505 to be replaced by a methionine (M). 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

0.082

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.89

CADD

Benign

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

MutationTaster

Benign

1.0

N;N;N

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

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

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