Genetic Variant NM_000898.5:c.496A>G (chrX-43797247-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

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

The NM_000898.5(MAOB):c.496A>G(p.Thr166Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,194,123 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000092 ( 0 hom. 4 hem. )

Consequence

MAOB
NM_000898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

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=0.26338333).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOB	NM_000898.5 link	c.496A>G	p.Thr166Ala	missense_variant	Exon 6 of 15	ENST00000378069.5	NP_000889.3	P27338-1
MAOB	XM_017029524.3 link	c.448A>G	p.Thr150Ala	missense_variant	Exon 6 of 15		XP_016885013.1	B7Z242

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOB	ENST00000378069.5 link	c.496A>G	p.Thr166Ala	missense_variant	Exon 6 of 15	1	NM_000898.5	ENSP00000367309.4		P27338-1
MAOB	ENST00000487544.1 link	n.822A>G		non_coding_transcript_exon_variant	Exon 7 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.0000720

AC:

AN:

111085

Hom.:

Cov.:

AF XY:

0.0000599

AC XY:

AN XY:

33395

show subpopulations

Gnomad AFR

AF:

0.000164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000236

AC:

AN:

169576

Hom.:

AF XY:

0.0000360

AC XY:

AN XY:

55570

show subpopulations

Gnomad AFR exome

AF:

0.000316

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000923

AC:

AN:

1083038

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

350572

show subpopulations

Gnomad4 AFR exome

AF:

0.000268

Gnomad4 AMR exome

AF:

0.0000296

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:

0.00000120

Gnomad4 OTH exome

AF:

0.0000220

GnomAD4 genome

AF:

0.0000720

AC:

AN:

111085

Hom.:

Cov.:

AF XY:

0.0000599

AC XY:

AN XY:

33395

show subpopulations

Gnomad4 AFR

AF:

0.000164

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.496A>G (p.T166A) alteration is located in exon 6 (coding exon 6) of the MAOB gene. This alteration results from a A to G substitution at nucleotide position 496, causing the threonine (T) at amino acid position 166 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

0.074

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.34

DEOGEN2

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.051

MetaRNN

Benign

0.26

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.34

Sift

Benign

0.74

Sift4G

Benign

0.73

Polyphen

0.021

Vest4

0.36

MVP

0.88

MPC

0.47

ClinPred

0.11

GERP RS

5.2

Varity_R

0.22

gMVP

0.65

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