Genetic Variant NM_000240.4:c.73+1702A>G (chrX-43658116-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000240.4(MAOA):c.73+1702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 10,443 control chromosomes in the GnomAD database, including 2,281 homozygotes. There are 1,403 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 19108 hom., 21927 hem., cov: 23)

Exomes 𝑓: 0.73 ( 2281 hom. 1403 hem. )

Failed GnomAD Quality Control

Consequence

MAOA
NM_000240.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0890

Publications

17 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4 link	c.73+1702A>G		intron_variant	Intron 1 of 14	ENST00000338702.4	NP_000231.1	P21397-1Q53YE7Q49A63
MAOA	NM_001270458.2 link	c.-327+147A>G		intron_variant	Intron 2 of 15		NP_001257387.1	P21397-2Q49A63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4 link	c.73+1702A>G		intron_variant	Intron 1 of 14	1	NM_000240.4	ENSP00000340684.3		P21397-1

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

76118

AN:

110289

Hom.:

19106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.687

GnomAD4 exome

AF:

0.728

AC:

7599

AN:

10443

Hom.:

2281

AF XY:

0.882

AC XY:

1403

AN XY:

1591

show subpopulations

African (AFR)

AF:

0.728

AC:

150

AN:

206

American (AMR)

AF:

0.550

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

AN:

East Asian (EAS)

AF:

0.381

AC:

AN:

South Asian (SAS)

AF:

0.385

AC:

AN:

208

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.773

AC:

AN:

European-Non Finnish (NFE)

AF:

0.739

AC:

7063

AN:

9555

Other (OTH)

AF:

0.676

AC:

211

AN:

312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

175

262

350

437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

264

528

792

1056

1320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.690

AC:

76158

AN:

110340

Hom.:

19108

Cov.:

AF XY:

0.672

AC XY:

21927

AN XY:

32606

show subpopulations

African (AFR)

AF:

0.741

AC:

22427

AN:

30257

American (AMR)

AF:

0.701

AC:

7289

AN:

10398

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

1811

AN:

2628

East Asian (EAS)

AF:

0.420

AC:

1464

AN:

3482

South Asian (SAS)

AF:

0.381

AC:

996

AN:

2616

European-Finnish (FIN)

AF:

0.563

AC:

3266

AN:

5802

Middle Eastern (MID)

AF:

0.712

AC:

153

AN:

215

European-Non Finnish (NFE)

AF:

0.706

AC:

37280

AN:

52770

Other (OTH)

AF:

0.684

AC:

1028

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

820

1640

2461

3281

4101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.696

Hom.:

5540

Bravo

AF:

0.702

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

(source)

DANN

Benign

0.49

PhyloP100

-0.089

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over