rs1555951370

Variant names:

• chrX-43744376-GC-AA
• rs1555951370
• NM_000240.4:c.1447_1448delGCinsAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000240.4(MAOA):​c.1447_1448delGCinsAA​(p.Ala483Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.0000109 in 2 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A483E) has been classified as Likely benign.

• Frequency: GnomAD MNV: 𝑓 0.000011 Genomes: not found (cov: 22)
• Consequence: MAOA NM_000240.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.1447_1448delGCinsAA	p.Ala483Lys	missense	N/A	NP_000231.1	Q53YE7
	MAOA	NM_001270458.2		c.1048_1049delGCinsAA	p.Ala350Lys	missense	N/A	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.1447_1448delGCinsAA	p.Ala483Lys	missense	N/A	ENSP00000340684.3	P21397-1
	MAOA	ENST00000967111.1		c.1510_1511delGCinsAA	p.Ala504Lys	missense	N/A	ENSP00000637170.1
	MAOA	ENST00000873971.1		c.1489_1490delGCinsAA	p.Ala497Lys	missense	N/A	ENSP00000544030.1

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

GnomAD MNV AF: 0.0000109 AC: 2 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.3

Splicing

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

Other links and lift over

dbSNP: rs1555951370; hg19: chrX-43603623;