X-43678961-A-G

Variant names:

• chrX-43678961-A-G
• rs1465108
• NM_000240.4:c.74-4552A>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.74-4552A>G 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 0.60 (14957 hom., 19270 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 21 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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.74-4552A>G		intron_variant	Intron 1 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.-326-4552A>G		intron_variant	Intron 2 of 15		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.74-4552A>G		intron_variant	Intron 1 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 66491 AN: 110471 Hom.: 14964 Cov.: 23

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.681

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.611

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: 0.602 AC: 66497 AN: 110522 Hom.: 14957 Cov.: 23 AF XY: 0.588 AC XY: 19270 AN XY: 32774

African (AFR) AF: 0.442 AC: 13461 AN: 30467

American (AMR) AF: 0.666 AC: 6850 AN: 10292

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 1785 AN: 2629

East Asian (EAS) AF: 0.421 AC: 1479 AN: 3514

South Asian (SAS) AF: 0.372 AC: 989 AN: 2661

European-Finnish (FIN) AF: 0.558 AC: 3233 AN: 5793

Middle Eastern (MID) AF: 0.684 AC: 147 AN: 215

European-Non Finnish (NFE) AF: 0.705 AC: 37194 AN: 52778

Other (OTH) AF: 0.608 AC: 912 AN: 1499

Alfa AF: 0.674 Hom.: 60984

Bravo AF: 0.604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		0.34
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: rs1465108; hg19: chrX-43538209;