Variant X-43803363-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_000898.5(MAOB):c.321G>T(p.Trp107Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,169,111 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000034 ( 0 hom. 12 hem. )

Consequence

MAOB
NM_000898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57

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 Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAOB	NM_000898.5 linkuse as main transcript	c.321G>T	p.Trp107Cys	missense_variant	4/15	ENST00000378069.5
MAOB	XM_017029524.3 linkuse as main transcript	c.273G>T	p.Trp91Cys	missense_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAOB	ENST00000378069.5 linkuse as main transcript	c.321G>T	p.Trp107Cys	missense_variant	4/15	1	NM_000898.5	P1	P27338-1
MAOB	ENST00000487544.1 linkuse as main transcript	n.647G>T		non_coding_transcript_exon_variant	5/7	5

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112127

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34325

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000692

AC:

AN:

144553

Hom.:

AF XY:

0.00

AC XY:

AN XY:

47011

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000144

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000341

AC:

AN:

1056984

Hom.:

Cov.:

AF XY:

0.0000352

AC XY:

AN XY:

340802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000385

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:

0.0000411

Gnomad4 OTH exome

AF:

0.0000225

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112127

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34325

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

Dec 27, 2023

The c.321G>T (p.W107C) alteration is located in exon 4 (coding exon 4) of the MAOB gene. This alteration results from a G to T substitution at nucleotide position 321, causing the tryptophan (W) at amino acid position 107 to be replaced by a cysteine (C). 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

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.49

Cadd

Uncertain

Dann

Benign

0.95

DEOGEN2

Pathogenic

0.93

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.57

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-8.8

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0060

Sift4G

Benign

0.17

Polyphen

0.97

Vest4

0.73

MutPred

0.69

Gain of sheet (P = 0.0266);

MVP

0.95

MPC

0.83

ClinPred

0.99

GERP RS

5.6

Varity_R

0.92

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.35

Position offset: 41

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