chrX-43733475-G-C

Variant names:

• chrX-43733475-G-C
• rs3027399
• NM_000240.4:c.1052+680G>C

Variant summary

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

The NM_000240.4(MAOA):​c.1052+680G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 111,575 control chromosomes in the GnomAD database, including 112 homozygotes. There are 1,321 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 0.043 (112 hom., 1321 hem., cov: 23)
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.1052+680G>C		intron_variant	Intron 9 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.653+680G>C		intron_variant	Intron 10 of 15		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.1052+680G>C		intron_variant	Intron 9 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 4756 AN: 111527 Hom.: 112 Cov.: 23

Gnomad AFR AF: 0.00865

Gnomad AMI AF: 0.00145

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0863

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0148

Gnomad FIN AF: 0.0278

Gnomad MID AF: 0.0551

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0481

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

GnomAD4 genome AF: 0.0426 AC: 4752 AN: 111575 Hom.: 112 Cov.: 23 AF XY: 0.0391 AC XY: 1321 AN XY: 33759

African (AFR) AF: 0.00863 AC: 265 AN: 30702

American (AMR) AF: 0.0353 AC: 372 AN: 10531

Ashkenazi Jewish (ASJ) AF: 0.0863 AC: 228 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3534

South Asian (SAS) AF: 0.0141 AC: 37 AN: 2618

European-Finnish (FIN) AF: 0.0278 AC: 169 AN: 6079

Middle Eastern (MID) AF: 0.0514 AC: 11 AN: 214

European-Non Finnish (NFE) AF: 0.0678 AC: 3597 AN: 53051

Other (OTH) AF: 0.0476 AC: 72 AN: 1514

Alfa AF: 0.0543 Hom.: 303

Bravo AF: 0.0409

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.49
PhyloP100		0.21
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: rs3027399; hg19: chrX-43592722;