rs6323

Variant names:

• chrX-43731789-G-T
• rs6323
• NM_000240.4:c.891G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_000240.4(MAOA):​c.891G>T​(p.Arg297Arg) 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 NM_000240.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.300
• Publications: 142 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: Benign. The variant received -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 VariationId is 92664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.3 with no splicing effect.

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.891G>T	p.Arg297Arg	synonymous	Exon 8 of 15	NP_000231.1	Q53YE7
	MAOA	NM_001270458.2		c.492G>T	p.Arg164Arg	synonymous	Exon 9 of 16	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.891G>T	p.Arg297Arg	synonymous	Exon 8 of 15	ENSP00000340684.3	P21397-1
	MAOA	ENST00000967111.1		c.891G>T	p.Arg297Arg	synonymous	Exon 8 of 15	ENSP00000637170.1
	MAOA	ENST00000873971.1		c.891G>T	p.Arg297Arg	synonymous	Exon 8 of 15	ENSP00000544030.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 79528 AN: 110183 Hom.: 21051 Cov.: 23

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

GnomAD2 exomes AF: 0.650 AC: 118872 AN: 182873 AF XY: 0.634

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 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

African (AFR) AF: 0.859 AC: 22677 AN: 26388

American (AMR) AF: 0.686 AC: 24119 AN: 35182

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 13981 AN: 19373

East Asian (EAS) AF: 0.427 AC: 12886 AN: 30176

South Asian (SAS) AF: 0.411 AC: 22251 AN: 54102

European-Finnish (FIN) AF: 0.619 AC: 25080 AN: 40500

Middle Eastern (MID) AF: 0.728 AC: 3008 AN: 4133

European-Non Finnish (NFE) AF: 0.707 AC: 594544 AN: 840618

Other (OTH) AF: 0.679 AC: 31270 AN: 46023

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

African (AFR) AF: 0.852 AC: 25817 AN: 30301

American (AMR) AF: 0.707 AC: 7290 AN: 10318

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 1867 AN: 2633

East Asian (EAS) AF: 0.425 AC: 1476 AN: 3476

South Asian (SAS) AF: 0.382 AC: 995 AN: 2605

European-Finnish (FIN) AF: 0.608 AC: 3496 AN: 5751

Middle Eastern (MID) AF: 0.743 AC: 159 AN: 214

European-Non Finnish (NFE) AF: 0.702 AC: 37029 AN: 52774

Other (OTH) AF: 0.712 AC: 1063 AN: 1492

Alfa AF: 0.717 Hom.: 88569

Bravo AF: 0.735

EpiCase AF: 0.709

EpiControl AF: 0.718

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Brunner syndrome (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
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

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

Other links and lift over

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