chrX-43731787-CGG-AGA

Variant names:

• chrX-43731787-CGG-AGA
• NM_000240.4:c.889_891delCGGinsAGA
• MAOA p.298

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_ModerateB4_Supporting

The NM_000240.4(MAOA):c.889_891delCGGinsAGA (p.298) variant causes a synonymous change. The gene MAOA is a tumor suppressor gene (CancerMine: 6 TSG, 1 oncogene, 2 driver citations). The gene MAOA is a known oncogene (CancerMine: 6 TSG, 1 oncogene, 2 driver citations). The gene MAOA is a cancer driver gene (CancerMine: 6 TSG, 1 oncogene, 2 driver citations). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 9.46). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: MAOA NM_000240.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.46
• 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: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])
	B4Synonymous/intronic, no splicing impact		Synonymous/intronic variant outside canonical splice sites (B4 supporting); Synonymous variant — splicing impact not confirmed absent; B4 supporting [-1]

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MAOA NM_000240.4	MANE Select	c.889_891delCGGinsAGA p.298	synonymous	N/A	Prot: NP_000231.1 UniProt:
	MAOA NM_001270458.2		c.490_492delCGGinsAGA p.165	synonymous	N/A	Prot: NP_001257387.1 UniProt:

MAOA NM_000240.4

MANE Select

HGVSc / HGVSpc.889_891delCGGinsAGAp.298

Exon rankN/A

synonymous

Prot: NP_000231.1UniProt: Q53YE7P21397-1

MAOA NM_001270458.2

HGVSc / HGVSpc.490_492delCGGinsAGAp.165

Exon rankN/A

synonymous

Prot: NP_001257387.1UniProt: P21397-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MAOA ENST00000338702.4	TSL:1MANE Select	c.889_891delCGGinsAGA p.298	synonymous	N/A	Prot: ENSP00000340684.3 UniProt:
	MAOA ENST00000967111.1		c.889_891delCGGinsAGA p.298	synonymous	N/A	Prot: ENSP00000637170.1 UniProt:
	MAOA ENST00000873971.1		c.889_891delCGGinsAGA p.298	synonymous	N/A	Prot: ENSP00000544030.1 UniProt:

MAOA ENST00000338702.4

TSL:1MANE Select

HGVSc / HGVSpc.889_891delCGGinsAGAp.298

Exon rankN/A

synonymous

Prot: ENSP00000340684.3UniProt: P21397-1

MAOA ENST00000967111.1

HGVSc / HGVSpc.889_891delCGGinsAGAp.298

Exon rankN/A

synonymous

Prot: ENSP00000637170.1UniProt: A0ACI8VKS4

MAOA ENST00000873971.1

HGVSc / HGVSpc.889_891delCGGinsAGAp.298

Exon rankN/A

synonymous

Prot: ENSP00000544030.1UniProt: A0ACI8R2S8

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:22
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:22

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Pathogenic	9.5

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chrX-43591034;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar