chrX-43693955-C-T

Variant names:

• chrX-43693955-C-T
• rs909525
• NM_000240.4:c.306+527C>T

Variant summary

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

The NM_000240.4(MAOA):​c.306+527C>T 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 0.66 (17474 hom., 20961 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• Publications: 30 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=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.306+527C>T		intron_variant	Intron 3 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.-94+527C>T		intron_variant	Intron 4 of 15		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.306+527C>T		intron_variant	Intron 3 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.660 AC: 72814 AN: 110291 Hom.: 17471 Cov.: 22

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.646

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: 0.660 AC: 72858 AN: 110346 Hom.: 17474 Cov.: 22 AF XY: 0.643 AC XY: 20961 AN XY: 32598

African (AFR) AF: 0.723 AC: 21902 AN: 30281

American (AMR) AF: 0.666 AC: 6904 AN: 10371

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 1637 AN: 2636

East Asian (EAS) AF: 0.423 AC: 1471 AN: 3481

South Asian (SAS) AF: 0.364 AC: 955 AN: 2622

European-Finnish (FIN) AF: 0.551 AC: 3222 AN: 5851

Middle Eastern (MID) AF: 0.617 AC: 132 AN: 214

European-Non Finnish (NFE) AF: 0.668 AC: 35222 AN: 52711

Other (OTH) AF: 0.643 AC: 970 AN: 1509

Alfa AF: 0.666 Hom.: 60096

Bravo AF: 0.672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.48
PhyloP100		0.39
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: rs909525; hg19: chrX-43553202;