X-43736253-G-C

Position:

• chrX-43736253-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000240.4(MAOA):​c.1079G>C​(p.Arg360Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: MAOA NM_000240.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOA	NM_000240.4	c.1079G>C	p.Arg360Pro	missense_variant	10/15	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.680G>C	p.Arg227Pro	missense_variant	11/16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.1079G>C	p.Arg360Pro	missense_variant	10/15	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	.;D
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.88	D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	-0.059	T
MutationAssessor	Uncertain	2.9	.;M
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.46
Sift	Benign	0.051	T;D
Sift4G	Benign	0.13	T;T
Polyphen		0.93	.;P
Vest4		0.40
MutPred		0.51		.;Loss of MoRF binding (P = 0.0021);
MVP		0.94
MPC		1.5
ClinPred		0.92	D
GERP RS		1.3
Varity_R		0.91
gMVP		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-43595500;