Variant X-43781451-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000898.5(MAOB):c.1022T>C(p.Met341Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000189 in 1,059,389 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000019 ( 0 hom. 1 hem. )

Consequence

MAOB
NM_000898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAOB	NM_000898.5 linkuse as main transcript	c.1022T>C	p.Met341Thr	missense_variant	9/15	ENST00000378069.5
MAOB	XM_017029524.3 linkuse as main transcript	c.974T>C	p.Met325Thr	missense_variant	9/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAOB	ENST00000378069.5 linkuse as main transcript	c.1022T>C	p.Met341Thr	missense_variant	9/15	1	NM_000898.5	P1	P27338-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000621

AC:

AN:

160929

Hom.:

AF XY:

0.00

AC XY:

AN XY:

49095

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:

0.0000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000189

AC:

AN:

1059389

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

331849

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000245

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 01, 2024

The c.1022T>C (p.M341T) alteration is located in exon 9 (coding exon 9) of the MAOB gene. This alteration results from a T to C substitution at nucleotide position 1022, causing the methionine (M) at amino acid position 341 to be replaced by a threonine (T). 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

0.33

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Pathogenic

0.92

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

0.10

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.59

Sift

Benign

0.097

Sift4G

Uncertain

0.011

Polyphen

0.024

Vest4

0.49

MutPred

0.68

Loss of sheet (P = 0.0126);

MVP

0.93

MPC

0.57

ClinPred

0.48

GERP RS

4.3

Varity_R

0.77

gMVP

0.88

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