Genetic Variant NM_001270458.2:c.-2051G>A (chrX-43654798-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001270458.2(MAOA):c.-2051G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 106 control chromosomes in the GnomAD database, including 7 homozygotes. There are 45 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 ( 19053 hom., 19938 hem., cov: 20)

Exomes 𝑓: 0.72 ( 7 hom. 45 hem. )

Failed GnomAD Quality Control

Consequence

MAOA
NM_001270458.2 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.784

Publications

12 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=-0.95).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_001270458.2 link	c.-2051G>A		upstream_gene_variant			NP_001257387.1	P21397-2Q49A63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000542639.6 link	c.-2051G>A		upstream_gene_variant		2		ENSP00000440846.1		P21397-2

Frequencies

GnomAD3 genomes

AF:

0.690

AC:

73963

AN:

107231

Hom.:

19051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.696

Gnomad ASJ

AF:

0.691

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.558

Gnomad MID

AF:

0.698

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.689

GnomAD4 exome

AF:

0.717

AC:

AN:

106

Hom.:

AF XY:

0.833

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.846

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.709

AC:

AN:

Other (OTH)

AF:

0.800

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.690

AC:

73997

AN:

107273

Hom.:

19053

Cov.:

AF XY:

0.670

AC XY:

19938

AN XY:

29761

show subpopulations

African (AFR)

AF:

0.740

AC:

21721

AN:

29347

American (AMR)

AF:

0.695

AC:

7030

AN:

10109

Ashkenazi Jewish (ASJ)

AF:

0.691

AC:

1789

AN:

2588

East Asian (EAS)

AF:

0.420

AC:

1398

AN:

3327

South Asian (SAS)

AF:

0.387

AC:

928

AN:

2395

European-Finnish (FIN)

AF:

0.558

AC:

2998

AN:

5375

Middle Eastern (MID)

AF:

0.704

AC:

143

AN:

203

European-Non Finnish (NFE)

AF:

0.705

AC:

36555

AN:

51822

Other (OTH)

AF:

0.686

AC:

1001

AN:

1459

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

783

1565

2348

3130

3913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.709

Hom.:

55932

Bravo

AF:

0.702

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.51

(source)

DANN

Benign

0.76

PhyloP100

-0.78

PromoterAI

-0.061

Neutral

(source)

Splicing

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