NM_000240.4:c.133C>T

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong

The NM_000240.4(MAOA):c.133C>T(p.Arg45Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,740 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R45Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAOA
NM_000240.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:3

Conservation

PhyloP100: 3.23

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Brunner syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

MAOA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.989

PP5

Variant X-43683572-C-T is Pathogenic according to our data. Variant chrX-43683572-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 208353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000240.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAOA	NM_000240.4	MANE Select	c.133C>T	p.Arg45Trp	missense	Exon 2 of 15	NP_000231.1	Q53YE7
MAOA	NM_001270458.2		c.-267C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 16	NP_001257387.1	P21397-2
MAOA	NM_001270458.2		c.-267C>T		5_prime_UTR	Exon 3 of 16	NP_001257387.1	P21397-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAOA	ENST00000338702.4	TSL:1 MANE Select	c.133C>T	p.Arg45Trp	missense	Exon 2 of 15	ENSP00000340684.3	P21397-1
MAOA	ENST00000542639.6	TSL:2	c.-267C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 16	ENSP00000440846.1	P21397-2
MAOA	ENST00000688006.1		c.-267C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000510311.1	P21397-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.13e-7

AC:

AN:

1095740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26372

American (AMR)

AF:

0.00

AC:

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19364

East Asian (EAS)

AF:

0.00

AC:

AN:

30183

South Asian (SAS)

AF:

0.00

AC:

AN:

54076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40509

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

839912

Other (OTH)

AF:

0.00

AC:

AN:

45996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Pathogenic/Likely pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Brunner syndrome (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Pathogenic

0.64

BayesDel_noAF

Pathogenic

0.68

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.95

FATHMM_MKL

Benign

0.76

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.85

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.9

PhyloP100

3.2

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.7

REVEL

Pathogenic

0.93

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.96

MutPred

0.85

Loss of methylation at R47 (P = 0.059)

MVP

1.0

MPC

1.7

ClinPred

1.0

GERP RS

3.6

Varity_R

0.98

gMVP

0.98

Mutation Taster

=21/79

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over