chrX-43665517-T-A

Variant names:

• chrX-43665517-T-A
• rs3788863
• NM_000240.4:c.73+9103T>A

Variant summary

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

The NM_000240.4(MAOA):​c.73+9103T>A 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 0.69 (19098 hom., 21657 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 3 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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.73+9103T>A		intron_variant	Intron 1 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.-327+7548T>A		intron_variant	Intron 2 of 15		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.73+9103T>A		intron_variant	Intron 1 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.690 AC: 75811 AN: 109939 Hom.: 19096 Cov.: 22

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.687

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: 0.690 AC: 75859 AN: 109998 Hom.: 19098 Cov.: 22 AF XY: 0.671 AC XY: 21657 AN XY: 32296

African (AFR) AF: 0.741 AC: 22392 AN: 30230

American (AMR) AF: 0.699 AC: 7175 AN: 10268

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 1813 AN: 2631

East Asian (EAS) AF: 0.422 AC: 1461 AN: 3464

South Asian (SAS) AF: 0.376 AC: 980 AN: 2603

European-Finnish (FIN) AF: 0.561 AC: 3223 AN: 5747

Middle Eastern (MID) AF: 0.690 AC: 147 AN: 213

European-Non Finnish (NFE) AF: 0.706 AC: 37195 AN: 52675

Other (OTH) AF: 0.684 AC: 1023 AN: 1495

Alfa AF: 0.706 Hom.: 4320

Bravo AF: 0.702

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		0.18
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: rs3788863; hg19: chrX-43524765;