dbSNP rs1803986: MAOA:p.Met445Ile (chrX-43743866-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000240.4(MAOA):c.1335G>T(p.Met445Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MAOA
NM_000240.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.55

Publications

3 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: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

MAOA links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4 link	c.1335G>T	p.Met445Ile	missense_variant	Exon 13 of 15	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2 link	c.936G>T	p.Met312Ile	missense_variant	Exon 14 of 16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4 link	c.1335G>T	p.Met445Ile	missense_variant	Exon 13 of 15	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1059723

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

346027

African (AFR)

AF:

0.00

AC:

AN:

25209

American (AMR)

AF:

0.00

AC:

AN:

29087

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18713

East Asian (EAS)

AF:

0.00

AC:

AN:

27688

South Asian (SAS)

AF:

0.00

AC:

AN:

50124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37965

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4092

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

822257

Other (OTH)

AF:

0.00

AC:

AN:

44588

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.53

BayesDel_noAF

Pathogenic

0.52

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

.;D

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

M_CAP

Pathogenic

0.74

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Uncertain

0.78

MutationAssessor

Benign

1.9

.;L

PhyloP100

9.6

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.5

D;D

REVEL

Pathogenic

0.89

Sift

Benign

0.078

T;T

Sift4G

Uncertain

0.028

D;T

Polyphen

0.93

.;P

Vest4

0.77

MutPred

0.69

.;Loss of ubiquitination at K440 (P = 0.0609);

MVP

0.99

MPC

1.7

ClinPred

0.96

GERP RS

5.9

Varity_R

0.90

gMVP

0.99

Mutation Taster

=37/63

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over