X-43728621-C-T

Variant names:

• chrX-43728621-C-T
• rs3810709
• NM_000240.4:c.645+307C>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.645+307C>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 0.54 (12423 hom., 17795 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000240.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOA	NM_000240.4	MANE Select	c.645+307C>T		intron	N/A	NP_000231.1	Q53YE7
	MAOA	NM_001270458.2		c.246+307C>T		intron	N/A	NP_001257387.1	P21397-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAOA	ENST00000338702.4	TSL:1 MANE Select	c.645+307C>T		intron	N/A	ENSP00000340684.3	P21397-1
	MAOA	ENST00000967111.1		c.645+307C>T		intron	N/A	ENSP00000637170.1
	MAOA	ENST00000873971.1		c.645+307C>T		intron	N/A	ENSP00000544030.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 60300 AN: 110744 Hom.: 12434 Cov.: 23

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.558

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: 0.544 AC: 60297 AN: 110796 Hom.: 12423 Cov.: 23 AF XY: 0.538 AC XY: 17795 AN XY: 33064

African (AFR) AF: 0.329 AC: 10041 AN: 30547

American (AMR) AF: 0.624 AC: 6496 AN: 10405

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 1658 AN: 2644

East Asian (EAS) AF: 0.422 AC: 1474 AN: 3490

South Asian (SAS) AF: 0.358 AC: 956 AN: 2672

European-Finnish (FIN) AF: 0.597 AC: 3468 AN: 5805

Middle Eastern (MID) AF: 0.628 AC: 135 AN: 215

European-Non Finnish (NFE) AF: 0.660 AC: 34856 AN: 52837

Other (OTH) AF: 0.556 AC: 841 AN: 1513

Alfa AF: 0.615 Hom.: 60219

Bravo AF: 0.538

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.73
PhyloP100		-0.99
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: rs3810709; hg19: chrX-43587868; COSMIC: COSV58643165;