rs772161607

Variant names:

• chrX-43742033-G-A
• rs772161607
• NM_000240.4:c.1248G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-43742033-G-A
• chrX-43742033-G-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_000240.4(MAOA):​c.1248G>A​(p.Met416Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 1,209,823 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., 7 hem., cov: 24)
  • Exomes 𝑓: 0.000015 (0 hom. 7 hem.)
• Consequence: MAOA NM_000240.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:1
• Conservation: PhyloP100: 3.36
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.081671).
• BP6: Variant X-43742033-G-A is Benign according to our data. Variant chrX-43742033-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 282807.
• BS2: High Hemizygotes in GnomAd4 at 7 XL gene

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.1248G>A	p.Met416Ile	missense	Exon 12 of 15	NP_000231.1	Q53YE7
	MAOA	NM_001270458.2		c.849G>A	p.Met283Ile	missense	Exon 13 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.1248G>A	p.Met416Ile	missense	Exon 12 of 15	ENSP00000340684.3	P21397-1
	MAOA	ENST00000967111.1		c.1248G>A	p.Met416Ile	missense	Exon 12 of 15	ENSP00000637170.1
	MAOA	ENST00000873971.1		c.1290G>A	p.Met430Ile	missense	Exon 12 of 15	ENSP00000544030.1

Frequencies

GnomAD3 genomes AF: 0.000161 AC: 18 AN: 111744 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000522

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000657 AC: 12 AN: 182756 AF XY: 0.000119

Gnomad AFR exome AF: 0.000533

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.0000155 AC: 17 AN: 1098027 Hom.: 0 Cov.: 36 AF XY: 0.0000193 AC XY: 7 AN XY: 363429

African (AFR) AF: 0.000341 AC: 9 AN: 26403

American (AMR) AF: 0.000114 AC: 4 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.00 AC: 0 AN: 54097

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40493

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842040

Other (OTH) AF: 0.0000868 AC: 4 AN: 46088

GnomAD4 genome AF: 0.000161 AC: 18 AN: 111796 Hom.: 0 Cov.: 24 AF XY: 0.000206 AC XY: 7 AN XY: 33982

African (AFR) AF: 0.000521 AC: 16 AN: 30732

American (AMR) AF: 0.000190 AC: 2 AN: 10518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.00 AC: 0 AN: 2647

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53220

Other (OTH) AF: 0.00 AC: 0 AN: 1512

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000155

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Uncertain	0.011	D
Sift4G	Benign	0.085	T
Polyphen		0.34	B
Vest4		0.35
MutPred		0.56		Loss of MoRF binding (P = 0.0935)
MVP		0.46
MPC		0.91
ClinPred		0.092	T
GERP RS		5.9
Varity_R		0.86
gMVP		0.96
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs772161607; hg19: chrX-43601280;