rs12843268

Variant names:

• chrX-43714419-A-G
• rs12843268
• NM_000240.4:c.503+1623A>G

Variant summary

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

The NM_000240.4(MAOA):​c.503+1623A>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 0.57 (13637 hom., 17389 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 12 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=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.503+1623A>G		intron_variant	Intron 5 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.104+1623A>G		intron_variant	Intron 6 of 15		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.503+1623A>G		intron_variant	Intron 5 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.566 AC: 61649 AN: 108942 Hom.: 13648 Cov.: 21

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.591

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: 0.566 AC: 61649 AN: 108994 Hom.: 13637 Cov.: 21 AF XY: 0.555 AC XY: 17389 AN XY: 31344

African (AFR) AF: 0.325 AC: 9744 AN: 29946

American (AMR) AF: 0.647 AC: 6597 AN: 10191

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 1811 AN: 2608

East Asian (EAS) AF: 0.417 AC: 1411 AN: 3381

South Asian (SAS) AF: 0.365 AC: 915 AN: 2509

European-Finnish (FIN) AF: 0.604 AC: 3428 AN: 5678

Middle Eastern (MID) AF: 0.712 AC: 148 AN: 208

European-Non Finnish (NFE) AF: 0.695 AC: 36350 AN: 52316

Other (OTH) AF: 0.588 AC: 879 AN: 1494

Alfa AF: 0.659 Hom.: 46986

Bravo AF: 0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.35
PhyloP100		-1.1
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: rs12843268; hg19: chrX-43573666;