rs587777457

Positions:

• chrX-43731695-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP5

The NM_000240.4(MAOA):​c.797G>T​(p.Cys266Phe) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAOA NM_000240.4 missense, splice_region
• Scores: Splicing: ADA: 0.9649
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.64

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a mutagenesis_site No loss of activity. (size 0) in uniprot entity AOFA_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-43731695-G-T is Pathogenic according to our data. Variant chrX-43731695-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 139432.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOA	NM_000240.4	c.797G>T	p.Cys266Phe	missense_variant, splice_region_variant	8/15	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.398G>T	p.Cys133Phe	missense_variant, splice_region_variant	9/16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.797G>T	p.Cys266Phe	missense_variant, splice_region_variant	8/15	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Brunner syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	.;D
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.93	.;P
Vest4		0.47
MutPred		0.71		.;Loss of methylation at K267 (P = 0.0376);
MVP		0.89
MPC		1.9
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.97
gMVP		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.96
dbscSNV1_RF	Pathogenic	0.72
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs587777457; hg19: chrX-43590942;