rs3027396

Variant names:

• chrX-43695425-C-T
• rs3027396
• NM_000240.4:c.306+1997C>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+1997C>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 0.65 (16900 hom., 20975 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• 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=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.306+1997C>T		intron_variant	Intron 3 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.-94+1997C>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+1997C>T		intron_variant	Intron 3 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.651 AC: 72017 AN: 110602 Hom.: 16900 Cov.: 23

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.630

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: 0.651 AC: 72051 AN: 110658 Hom.: 16900 Cov.: 23 AF XY: 0.637 AC XY: 20975 AN XY: 32924

African (AFR) AF: 0.690 AC: 20950 AN: 30357

American (AMR) AF: 0.663 AC: 6903 AN: 10416

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 1633 AN: 2629

East Asian (EAS) AF: 0.421 AC: 1467 AN: 3486

South Asian (SAS) AF: 0.366 AC: 977 AN: 2669

European-Finnish (FIN) AF: 0.552 AC: 3226 AN: 5840

Middle Eastern (MID) AF: 0.621 AC: 131 AN: 211

European-Non Finnish (NFE) AF: 0.669 AC: 35372 AN: 52868

Other (OTH) AF: 0.627 AC: 944 AN: 1506

Alfa AF: 0.669 Hom.: 39344

Bravo AF: 0.660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.33
DANN	Benign	0.55
PhyloP100		-0.77
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: rs3027396; hg19: chrX-43554672;