X-43728621-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000240.4(MAOA):c.645+307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.54 (12423 hom., 17795 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd at 12434 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAOA	NM_000240.4	c.645+307C>T		intron_variant		ENST00000338702.4
MAOA	NM_001270458.2	c.246+307C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAOA	ENST00000338702.4	c.645+307C>T		intron_variant		1	NM_000240.4	P1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 60300 AN: 110744 Hom.: 12434 Cov.: 23 AF XY: 0.539 AC XY: 17782 AN XY: 33002

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.558

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.544 AC: 60297 AN: 110796 Hom.: 12423 Cov.: 23 AF XY: 0.538 AC XY: 17795 AN XY: 33064

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.556

Alfa AF: 0.641 Hom.: 49030

Bravo AF: 0.538

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.67
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs3810709; hg19: chrX-43587868; COSMIC: COSV58643165;