rs2235186

Variant names:

• chrX-43736181-A-G
• rs2235186
• NM_000240.4:c.1053-46A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-43736181-A-G
• chrX-43736181-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• Brunner syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000240.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOA	NM_000240.4	MANE Select	c.1053-46A>G		intron	N/A	NP_000231.1
	MAOA	NM_001270458.2		c.654-46A>G		intron	N/A	NP_001257387.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOA	ENST00000338702.4	TSL:1 MANE Select	c.1053-46A>G		intron	N/A	ENSP00000340684.3
	MAOA	ENST00000693128.1		c.948-46A>G		intron	N/A	ENSP00000508493.1
	MAOA	ENST00000542639.6	TSL:2	c.654-46A>G		intron	N/A	ENSP00000440846.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 79733 AN: 110381 Hom.: 21059 Cov.: 23

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

GnomAD2 exomes AF: 0.655 AC: 107714 AN: 164503 AF XY: 0.642

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 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

African (AFR) AF: 0.863 AC: 19757 AN: 22884

American (AMR) AF: 0.687 AC: 23044 AN: 33522

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 12690 AN: 17535

East Asian (EAS) AF: 0.428 AC: 11930 AN: 27843

South Asian (SAS) AF: 0.416 AC: 20341 AN: 48934

European-Finnish (FIN) AF: 0.620 AC: 23631 AN: 38103

Middle Eastern (MID) AF: 0.734 AC: 2718 AN: 3701

European-Non Finnish (NFE) AF: 0.712 AC: 485157 AN: 681048

Other (OTH) AF: 0.685 AC: 26766 AN: 39061

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

African (AFR) AF: 0.852 AC: 25846 AN: 30334

American (AMR) AF: 0.709 AC: 7361 AN: 10383

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 1873 AN: 2631

East Asian (EAS) AF: 0.425 AC: 1469 AN: 3458

South Asian (SAS) AF: 0.381 AC: 1007 AN: 2640

European-Finnish (FIN) AF: 0.609 AC: 3549 AN: 5828

Middle Eastern (MID) AF: 0.740 AC: 159 AN: 215

European-Non Finnish (NFE) AF: 0.702 AC: 37053 AN: 52760

Other (OTH) AF: 0.715 AC: 1085 AN: 1517

Alfa AF: 0.713 Hom.: 77457

Bravo AF: 0.736

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.51
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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