X-43688062-A-G

Variant names:

• chrX-43688062-A-G
• rs5906957
• NM_000240.4:c.168+4455A>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.168+4455A>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 0.71 (20180 hom., 22926 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 22 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=-0.86).

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.168+4455A>G		intron	N/A	NP_000231.1
	MAOA	NM_001270458.2		c.-232+4455A>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.168+4455A>G		intron	N/A	ENSP00000340684.3
	MAOA	ENST00000693128.1		c.168+4455A>G		intron	N/A	ENSP00000508493.1
	MAOA	ENST00000542639.6	TSL:2	c.-232+4455A>G		intron	N/A	ENSP00000440846.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 78597 AN: 110862 Hom.: 20185 Cov.: 23

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.714

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.713

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: 0.709 AC: 78625 AN: 110915 Hom.: 20180 Cov.: 23 AF XY: 0.691 AC XY: 22926 AN XY: 33171

African (AFR) AF: 0.704 AC: 21447 AN: 30454

American (AMR) AF: 0.717 AC: 7482 AN: 10440

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 1871 AN: 2639

East Asian (EAS) AF: 0.419 AC: 1469 AN: 3509

South Asian (SAS) AF: 0.411 AC: 1090 AN: 2650

European-Finnish (FIN) AF: 0.615 AC: 3620 AN: 5882

Middle Eastern (MID) AF: 0.710 AC: 154 AN: 217

European-Non Finnish (NFE) AF: 0.755 AC: 39980 AN: 52948

Other (OTH) AF: 0.709 AC: 1065 AN: 1502

Alfa AF: 0.736 Hom.: 47671

Bravo AF: 0.717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.76
PhyloP100		-0.078
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: rs5906957; hg19: chrX-43547310;