X-43733475-G-C

Position:

• chrX-43733475-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000240.4(MAOA):​c.1052+680G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 111,575 control chromosomes in the GnomAD database, including 112 homozygotes. There are 1,321 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.043 (112 hom., 1321 hem., cov: 23)
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAOA	NM_000240.4	c.1052+680G>C		intron_variant		ENST00000338702.4
MAOA	NM_001270458.2	c.653+680G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAOA	ENST00000338702.4	c.1052+680G>C		intron_variant		1	NM_000240.4	P1

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 4756 AN: 111527 Hom.: 112 Cov.: 23 AF XY: 0.0392 AC XY: 1322 AN XY: 33701

Gnomad AFR AF: 0.00865

Gnomad AMI AF: 0.00145

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0863

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0148

Gnomad FIN AF: 0.0278

Gnomad MID AF: 0.0551

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0426 AC: 4752 AN: 111575 Hom.: 112 Cov.: 23 AF XY: 0.0391 AC XY: 1321 AN XY: 33759

Gnomad4 AFR AF: 0.00863

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0863

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0278

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.0476

Alfa AF: 0.0543 Hom.: 303

Bravo AF: 0.0409

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs3027399; hg19: chrX-43592722;