Genetic Variant MAOA:c.-1673_-1644dupAGTACCCGCACCAGTACCGGCACCGGCACC (chrX-43655100-C-CACCGGCACCGGCACCAGTACCCGCACCAGT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001270458.2(MAOA):c.-1673_-1644dupAGTACCCGCACCAGTACCGGCACCGGCACC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 61,976 control chromosomes in the GnomAD database, including 30 homozygotes. There are 2 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0079 ( 30 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.00065 ( 1 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MAOA
NM_001270458.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.449

Publications

1 publications found

Variant links:

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)

MAOA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 30 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_001270458.2 link	c.-1673_-1644dupAGTACCCGCACCAGTACCGGCACCGGCACC		5_prime_UTR_variant	Exon 1 of 16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000542639.6 link	c.-1673_-1644dupAGTACCCGCACCAGTACCGGCACCGGCACC		5_prime_UTR_variant	Exon 1 of 16	2		ENSP00000440846.1

Frequencies

GnomAD3 genomes

AF:

0.00783

AC:

485

AN:

61935

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00553

Gnomad AMI

AF:

0.00890

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00693

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.00156

Gnomad FIN

AF:

0.00335

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00727

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000653

AC:

AN:

3062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

1330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000896

AC:

AN:

2231

Other (OTH)

AF:

0.00

AC:

AN:

112

GnomAD4 genome

AF:

0.00786

AC:

487

AN:

61976

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

19116

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00557

AC:

106

AN:

19037

American (AMR)

AF:

0.00651

AC:

AN:

5375

Ashkenazi Jewish (ASJ)

AF:

0.00693

AC:

AN:

1443

East Asian (EAS)

AF:

0.00175

AC:

AN:

2284

South Asian (SAS)

AF:

0.00157

AC:

AN:

1915

European-Finnish (FIN)

AF:

0.00335

AC:

AN:

3580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

103

European-Non Finnish (NFE)

AF:

0.0114

AC:

308

AN:

27060

Other (OTH)

AF:

0.00713

AC:

AN:

842

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.387

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00840

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.45

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over