rs2239448

Variant names:

• chrX-43743432-T-C
• rs2239448
• NM_000240.4:c.1263-362T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-43743432-T-C
• chrX-43743432-T-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.1263-362T>C 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 0.65 (16899 hom., 19429 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 9 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=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.1263-362T>C		intron_variant	Intron 12 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.864-362T>C		intron_variant	Intron 13 of 15		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.1263-362T>C		intron_variant	Intron 12 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.649 AC: 70396 AN: 108498 Hom.: 16902 Cov.: 21

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.727

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.655

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: 0.649 AC: 70426 AN: 108555 Hom.: 16899 Cov.: 21 AF XY: 0.628 AC XY: 19429 AN XY: 30957

African (AFR) AF: 0.620 AC: 18476 AN: 29777

American (AMR) AF: 0.627 AC: 6451 AN: 10281

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 1865 AN: 2610

East Asian (EAS) AF: 0.419 AC: 1445 AN: 3445

South Asian (SAS) AF: 0.362 AC: 857 AN: 2369

European-Finnish (FIN) AF: 0.605 AC: 3423 AN: 5660

Middle Eastern (MID) AF: 0.734 AC: 152 AN: 207

European-Non Finnish (NFE) AF: 0.700 AC: 36426 AN: 52074

Other (OTH) AF: 0.652 AC: 956 AN: 1467

Alfa AF: 0.677 Hom.: 5325

Bravo AF: 0.651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.99
DANN	Benign	0.44
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: rs2239448; hg19: chrX-43602679;