chrX-43736496-A-G

Variant names:

• chrX-43736496-A-G
• rs2235185
• NM_000240.4:c.1106+216A>G

Variant summary

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

The ENST00000338702.4(MAOA):​c.1106+216A>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 (21058 hom., 22692 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: MAOA ENST00000338702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 7 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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000338702.4. 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.1106+216A>G		intron	N/A	NP_000231.1
	MAOA	NM_001270458.2		c.707+216A>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.1106+216A>G		intron	N/A	ENSP00000340684.3
	MAOA	ENST00000686980.1		n.1454A>G		non_coding_transcript_exon	Exon 10 of 14
	MAOA	ENST00000693128.1		c.1001+216A>G		intron	N/A	ENSP00000508493.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 79416 AN: 109949 Hom.: 21058 Cov.: 22

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.716

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.722 AC: 79458 AN: 110004 Hom.: 21058 Cov.: 22 AF XY: 0.704 AC XY: 22692 AN XY: 32250

African (AFR) AF: 0.852 AC: 25805 AN: 30291

American (AMR) AF: 0.710 AC: 7275 AN: 10248

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 1867 AN: 2627

East Asian (EAS) AF: 0.428 AC: 1479 AN: 3456

South Asian (SAS) AF: 0.379 AC: 987 AN: 2604

European-Finnish (FIN) AF: 0.607 AC: 3458 AN: 5694

Middle Eastern (MID) AF: 0.746 AC: 159 AN: 213

European-Non Finnish (NFE) AF: 0.702 AC: 36994 AN: 52717

Other (OTH) AF: 0.711 AC: 1055 AN: 1483

Alfa AF: 0.692 Hom.: 11476

Bravo AF: 0.736

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.33
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: rs2235185; hg19: chrX-43595743;