rs3027405

Variant names:

• chrX-43737082-A-T
• rs3027405
• NM_000240.4:c.1106+802A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000240.4(MAOA):​c.1106+802A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 111,741 control chromosomes in the GnomAD database, including 734 homozygotes. There are 2,850 hemizygotes in GnomAD. 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 0.096 (734 hom., 2850 hem., cov: 22)
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.1106+802A>T		intron_variant	Intron 10 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.707+802A>T		intron_variant	Intron 11 of 15		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.1106+802A>T		intron_variant	Intron 10 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.0959 AC: 10713 AN: 111686 Hom.: 733 Cov.: 22

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0733

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0962

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0823

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

GnomAD4 genome AF: 0.0961 AC: 10736 AN: 111741 Hom.: 734 Cov.: 22 AF XY: 0.0840 AC XY: 2850 AN XY: 33937

African (AFR) AF: 0.244 AC: 7485 AN: 30642

American (AMR) AF: 0.0527 AC: 555 AN: 10536

Ashkenazi Jewish (ASJ) AF: 0.0733 AC: 194 AN: 2646

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3551

South Asian (SAS) AF: 0.0209 AC: 56 AN: 2675

European-Finnish (FIN) AF: 0.0141 AC: 86 AN: 6109

Middle Eastern (MID) AF: 0.101 AC: 22 AN: 218

European-Non Finnish (NFE) AF: 0.0415 AC: 2204 AN: 53156

Other (OTH) AF: 0.0813 AC: 124 AN: 1526

Alfa AF: 0.0748 Hom.: 393

Bravo AF: 0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.19
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: rs3027405; hg19: chrX-43596329;