X-43731787-C-A

Variant names:

• chrX-43731787-C-A
• NM_000240.4:c.889C>A
• MAOA p.Arg297Arg

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 0 classification points (ACMG Germline Pathogenicity v2019). PM2BP4BP7

The NM_000240.4(MAOA):c.889C>A (p.Arg297Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) 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: 22)
• Consequence: MAOA NM_000240.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.53
• 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 ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 0 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD/XL) (threshold 0.0001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Supporting).
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

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.889C>A p.Arg297Arg	synonymous	Exon 8 of 15	Prot: NP_000231.1 UniProt:
	MAOA NM_001270458.2		c.490C>A p.Arg164Arg	synonymous	Exon 9 of 16	Prot: NP_001257387.1 UniProt:

MAOA NM_000240.4

MANE Select

HGVSc / HGVSpc.889C>Ap.Arg297Arg

Exon rankExon 8 of 15

synonymous

Prot: NP_000231.1UniProt: Q53YE7P21397-1

MAOA NM_001270458.2

HGVSc / HGVSpc.490C>Ap.Arg164Arg

Exon rankExon 9 of 16

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.889C>A p.Arg297Arg	synonymous	Exon 8 of 15	Prot: ENSP00000340684.3 UniProt:
	MAOA ENST00000967111.1		c.889C>A p.Arg297Arg	synonymous	Exon 8 of 15	Prot: ENSP00000637170.1 UniProt:
	MAOA ENST00000873971.1		c.889C>A p.Arg297Arg	synonymous	Exon 8 of 15	Prot: ENSP00000544030.1 UniProt:

MAOA ENST00000338702.4

TSL:1MANE Select

HGVSc / HGVSpc.889C>Ap.Arg297Arg

Exon rankExon 8 of 15

synonymous

Prot: ENSP00000340684.3UniProt: P21397-1

MAOA ENST00000967111.1

HGVSc / HGVSpc.889C>Ap.Arg297Arg

Exon rankExon 8 of 15

synonymous

Prot: ENSP00000637170.1UniProt: A0ACI8VKS4

MAOA ENST00000873971.1

HGVSc / HGVSpc.889C>Ap.Arg297Arg

Exon rankExon 8 of 15

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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:22
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:30
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:22

Showing 3 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.0000772	1	12950	0.00	0	23216

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	20
BayesDel_noAF	Benign	-0.10
CADD	Benign	11
DANN	Benign	0.70
GPN-Star LLR	N/A	-4.2
GPN-Star score	N/A	4.2
PhyloP100	Uncertain	5.5

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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