chrX-43728184-G-A

Position:

chrX-43728184-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000240.4(MAOA):c.515G>A(p.Arg172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000419 in 1,208,915 control chromosomes in the GnomAD database, including 2 homozygotes. There are 145 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., 58 hem., cov: 24)

Exomes 𝑓: 0.00025 ( 2 hom. 87 hem. )

Consequence

MAOA
NM_000240.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

MAOA (HGNC:6833): (monoamine oxidase A) This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. Mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]

MAOA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006507039).

BP6

Variant X-43728184-G-A is Benign according to our data. Variant chrX-43728184-G-A is described in ClinVar as [Benign]. Clinvar id is 435814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-43728184-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 58 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOA	NM_000240.4 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	6/15	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	7/16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	6/15	1	NM_000240.4	ENSP00000340684	P1	P21397-1

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

228

AN:

111652

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

AN XY:

33834

show subpopulations

Gnomad AFR

AF:

0.00685

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00142

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:

0.0000376

Gnomad OTH

AF:

0.000667

GnomAD3 exomes

AF:

0.000622

AC:

114

AN:

183193

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

67701

show subpopulations

Gnomad AFR exome

AF:

0.00730

Gnomad AMR exome

AF:

0.000437

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000253

AC:

278

AN:

1097212

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

362620

show subpopulations

Gnomad4 AFR exome

AF:

0.00800

Gnomad4 AMR exome

AF:

0.000511

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00000832

Gnomad4 OTH exome

AF:

0.000608

GnomAD4 genome

AF:

0.00204

AC:

228

AN:

111703

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

AN XY:

33895

show subpopulations

Gnomad4 AFR

AF:

0.00683

Gnomad4 AMR

AF:

0.00142

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.000658

Alfa

AF:

0.000346

Hom.:

Bravo

AF:

0.00286

ESP6500AA

AF:

0.00600

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000585

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 30, 2016

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2017

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

MAOA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Brunner syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.0

DANN

Benign

0.55

DEOGEN2

Uncertain

0.43

.;T

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.077

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.075

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.074

Sift

Benign

0.94

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0010

.;B

Vest4

0.034

MVP

0.66

MPC

0.78

ClinPred

0.0021

GERP RS

-2.7

Varity_R

0.083

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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