X-43655100-CACCGGCACCGGCACCAGTACCCGCACCAGTACCGGCACCGGCACCAGTACCCGCACCAGT-CACCGGCACCGGCACCAGTACCCGCACCAGT

Position:

• chrX-43655100-CACCGGCACCGGCACCAGTACCCGCACCAGTACCGGCACCGGCACCAGTACCCGCACCAGT-CACCGGCACCGGCACCAGTACCCGCACCAGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001270458.2(MAOA):​c.-1673_-1644del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 62,032 control chromosomes in the GnomAD database, including 28 homozygotes. There are 120 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (28 hom., 120 hem., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_001270458.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (758/62032) while in subpopulation AFR AF= 0.0346 (659/19033). AF 95% confidence interval is 0.0324. There are 28 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOA	NM_001270458.2	c.-1673_-1644del		5_prime_UTR_variant	1/16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000542639.6	c.-1673_-1644del		5_prime_UTR_variant	1/16	2		ENSP00000440846

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 758 AN: 61991 Hom.: 28 Cov.: 24 AF XY: 0.00629 AC XY: 120 AN XY: 19073

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.00554

Gnomad EAS AF: 0.00741

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.00848

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 3062 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1330

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0122 AC: 758 AN: 62032 Hom.: 28 Cov.: 24 AF XY: 0.00628 AC XY: 120 AN XY: 19112

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.00390

Gnomad4 ASJ AF: 0.00554

Gnomad4 EAS AF: 0.00744

Gnomad4 SAS AF: 0.00209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00148

Gnomad4 OTH AF: 0.00831

Alfa AF: 0.00668 Hom.: 65

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1346551029; hg19: chrX-43514348;