X-43683507-C-A

Variant names:

• chrX-43683507-C-A
• rs1196492976
• NM_000240.4:c.74-6C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000240.4(MAOA):​c.74-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000919 in 1,088,683 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
• Consequence: MAOA NM_000240.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002661
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.74-6C>A		splice_region intron	N/A	NP_000231.1	Q53YE7
	MAOA	NM_001270458.2		c.-326-6C>A		splice_region 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.74-6C>A		splice_region intron	N/A	ENSP00000340684.3	P21397-1
	MAOA	ENST00000967111.1		c.74-6C>A		splice_region intron	N/A	ENSP00000637170.1
	MAOA	ENST00000873971.1		c.74-6C>A		splice_region intron	N/A	ENSP00000544030.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.19e-7 AC: 1 AN: 1088683 Hom.: 0 Cov.: 28 AF XY: 0.00000282 AC XY: 1 AN XY: 354939

African (AFR) AF: 0.00 AC: 0 AN: 26187

American (AMR) AF: 0.00 AC: 0 AN: 35130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19311

East Asian (EAS) AF: 0.00 AC: 0 AN: 30153

South Asian (SAS) AF: 0.00 AC: 0 AN: 53854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4115

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 833705

Other (OTH) AF: 0.00 AC: 0 AN: 45738

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.31
PhyloP100		0.018

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.076
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: rs1196492976; hg19: chrX-43542755;