rs1135401773
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_000240.4(MAOA):c.730G>A(p.Val244Ile) 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. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. V244V) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 23)
Consequence
MAOA
NM_000240.4 missense
NM_000240.4 missense
Scores
7
1
7
Clinical Significance
Conservation
PhyloP100: 9.32
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.987
PP5
?
Variant X-43731325-G-A is Pathogenic according to our data. Variant chrX-43731325-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 431096.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-43731325-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAOA | NM_000240.4 | c.730G>A | p.Val244Ile | missense_variant | 7/15 | ENST00000338702.4 | |
MAOA | NM_001270458.2 | c.331G>A | p.Val111Ile | missense_variant | 8/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAOA | ENST00000338702.4 | c.730G>A | p.Val244Ile | missense_variant | 7/15 | 1 | NM_000240.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brunner syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Aug 01, 2017 | Missense Variant in the MAOA gene identified in a male, 7 y with speech delay, moderate ID and behavioral anomalies. The healthy mother had a XI of 82%. The variant affects a highly conserved aminoacid which is located in close proximity to the other described missense variants affecting MAOA function. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Benign
D;D
Sift4G
Benign
T;D
Polyphen
0.99
.;D
Vest4
MutPred
0.92
.;Loss of loop (P = 0.1242);
MVP
MPC
1.5
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at