rs2235186

chrX-43736181-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000240.4(MAOA):c.1053-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.72 (21059 hom., 23000 hem., cov: 23)
  • Exomes 𝑓: 0.69 (157600 hom. 175455 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Homozygotes in GnomAd at 21059 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAOA	NM_000240.4	c.1053-46A>G		intron_variant		ENST00000338702.4
MAOA	NM_001270458.2	c.654-46A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAOA	ENST00000338702.4	c.1053-46A>G		intron_variant		1	NM_000240.4	P1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 79733 AN: 110381 Hom.: 21059 Cov.: 23 AF XY: 0.704 AC XY: 22952 AN XY: 32595

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.730

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.720

GnomAD3 exomes AF: 0.655 AC: 107714 AN: 164503 Hom.: 25283 AF XY: 0.642 AC XY: 33714 AN XY: 52521

Gnomad AFR exome AF: 0.858

Gnomad AMR exome AF: 0.681

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.434

Gnomad SAS exome AF: 0.403

Gnomad FIN exome AF: 0.625

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.674

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.686 AC: 626034 AN: 912631 Hom.: 157600 Cov.: 13 AF XY: 0.676 AC XY: 175455 AN XY: 259563

Gnomad4 AFR exome AF: 0.863

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.712

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.722 AC: 79777 AN: 110437 Hom.: 21059 Cov.: 23 AF XY: 0.704 AC XY: 23000 AN XY: 32661

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.715

Alfa AF: 0.704 Hom.: 53803

Bravo AF: 0.736

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.5
Dann	Benign	0.51

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: rs2235186; hg19: chrX-43595428; COSMIC: COSV58641061; COSMIC: COSV58641061;