rs1137070

Variant names:

• chrX-43744144-T-C
• rs1137070
• NM_000240.4:c.1410T>C

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.1410T>C​(p.Asp470Asp) 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 0.65 (16929 hom., 19972 hem., cov: 21)
  • Exomes 𝑓: 0.67 (171518 hom. 239866 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.140
• Publications: 113 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=-0.82).
• BP6: Variant X-43744144-T-C is Benign according to our data. Variant chrX-43744144-T-C is described in ClinVar as Benign. ClinVar VariationId is 92663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.14 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.1410T>C	p.Asp470Asp	synonymous	Exon 14 of 15	NP_000231.1	Q53YE7
	MAOA	NM_001270458.2		c.1011T>C	p.Asp337Asp	synonymous	Exon 15 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.1410T>C	p.Asp470Asp	synonymous	Exon 14 of 15	ENSP00000340684.3	P21397-1
	MAOA	ENST00000967111.1		c.1473T>C	p.Asp491Asp	synonymous	Exon 14 of 15	ENSP00000637170.1
	MAOA	ENST00000873971.1		c.1452T>C	p.Asp484Asp	synonymous	Exon 14 of 15	ENSP00000544030.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 71036 AN: 109333 Hom.: 16932 Cov.: 21

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.716

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.654

GnomAD2 exomes AF: 0.621 AC: 113389 AN: 182565 AF XY: 0.614

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.604

Gnomad ASJ exome AF: 0.714

Gnomad EAS exome AF: 0.431

Gnomad FIN exome AF: 0.625

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.648

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.673 AC: 738410 AN: 1096387 Hom.: 171518 Cov.: 36 AF XY: 0.662 AC XY: 239866 AN XY: 362221

African (AFR) AF: 0.616 AC: 16247 AN: 26370

American (AMR) AF: 0.610 AC: 21447 AN: 35170

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 14056 AN: 19377

East Asian (EAS) AF: 0.424 AC: 12787 AN: 30167

South Asian (SAS) AF: 0.405 AC: 21913 AN: 54105

European-Finnish (FIN) AF: 0.620 AC: 25088 AN: 40483

Middle Eastern (MID) AF: 0.705 AC: 2908 AN: 4127

European-Non Finnish (NFE) AF: 0.706 AC: 593606 AN: 840556

Other (OTH) AF: 0.659 AC: 30358 AN: 46032

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.650 AC: 71065 AN: 109385 Hom.: 16929 Cov.: 21 AF XY: 0.631 AC XY: 19972 AN XY: 31661

African (AFR) AF: 0.621 AC: 18634 AN: 29994

American (AMR) AF: 0.627 AC: 6394 AN: 10199

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 1877 AN: 2632

East Asian (EAS) AF: 0.423 AC: 1455 AN: 3438

South Asian (SAS) AF: 0.369 AC: 906 AN: 2458

European-Finnish (FIN) AF: 0.610 AC: 3490 AN: 5724

Middle Eastern (MID) AF: 0.726 AC: 156 AN: 215

European-Non Finnish (NFE) AF: 0.700 AC: 36809 AN: 52565

Other (OTH) AF: 0.650 AC: 971 AN: 1493

Alfa AF: 0.684 Hom.: 103944

Bravo AF: 0.651

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Brunner syndrome (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		0.14
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

Other links and lift over

dbSNP: rs1137070; hg19: chrX-43603391; COSMIC: COSV58641635;