rs6323

Positions:

• chrX-43731789-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The ENST00000338702.4(MAOA):​c.891G>T​(p.Arg297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (21051 hom., 22800 hem., cov: 23)
  • Exomes 𝑓: 0.68 (177110 hom. 243137 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAOA ENST00000338702.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.300

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant X-43731789-G-T is Benign according to our data. Variant chrX-43731789-G-T is described in ClinVar as [Benign]. Clinvar id is 92664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-43731789-G-T is described in Lovd as [Benign]. Variant chrX-43731789-G-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.3 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOA	NM_000240.4	c.891G>T	p.Arg297=	synonymous_variant	8/15	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.492G>T	p.Arg164=	synonymous_variant	9/16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.891G>T	p.Arg297=	synonymous_variant	8/15	1	NM_000240.4	ENSP00000340684	P1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 79528 AN: 110183 Hom.: 21051 Cov.: 23 AF XY: 0.703 AC XY: 22754 AN XY: 32385

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.717

GnomAD3 exomes AF: 0.650 AC: 118872 AN: 182873 Hom.: 26030 AF XY: 0.634 AC XY: 42749 AN XY: 67445

Gnomad AFR exome AF: 0.854

Gnomad AMR exome AF: 0.678

Gnomad ASJ exome AF: 0.711

Gnomad EAS exome AF: 0.431

Gnomad SAS exome AF: 0.398

Gnomad FIN exome AF: 0.623

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.668

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.684 AC: 749816 AN: 1096495 Hom.: 177110 Cov.: 34 AF XY: 0.671 AC XY: 243137 AN XY: 362185

Gnomad4 AFR exome AF: 0.859

Gnomad4 AMR exome AF: 0.686

Gnomad4 ASJ exome AF: 0.722

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.619

Gnomad4 NFE exome AF: 0.707

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.722 AC: 79570 AN: 110234 Hom.: 21051 Cov.: 23 AF XY: 0.703 AC XY: 22800 AN XY: 32446

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.712

Alfa AF: 0.705 Hom.: 69358

Bravo AF: 0.735

EpiCase AF: 0.709

EpiControl AF: 0.718

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 16, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Brunner syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.2
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs6323; hg19: chrX-43591036; COSMIC: COSV58641947; COSMIC: COSV58641947;