chrX-43744144-T-C

Position:

• chrX-43744144-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_000240.4(MAOA):​c.1410T>C​(p.Asp470=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (16929 hom., 19972 hem., cov: 21)
  • Exomes 𝑓: 0.67 (171518 hom. 239866 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.140

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-43744144-T-C is Benign according to our data. Variant chrX-43744144-T-C is described in ClinVar as [Benign]. Clinvar id is 92663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-43744144-T-C is described in Lovd as [Benign]. Variant chrX-43744144-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.14 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAOA	NM_000240.4	c.1410T>C	p.Asp470=	synonymous_variant	14/15	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.1011T>C	p.Asp337=	synonymous_variant	15/16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.1410T>C	p.Asp470=	synonymous_variant	14/15	1	NM_000240.4	ENSP00000340684	P1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 71036 AN: 109333 Hom.: 16932 Cov.: 21 AF XY: 0.631 AC XY: 19934 AN XY: 31599

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.716

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.654

GnomAD3 exomes AF: 0.621 AC: 113389 AN: 182565 Hom.: 23240 AF XY: 0.614 AC XY: 41272 AN XY: 67167

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.604

Gnomad ASJ exome AF: 0.714

Gnomad EAS exome AF: 0.431

Gnomad SAS exome AF: 0.391

Gnomad FIN exome AF: 0.625

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.648

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.673 AC: 738410 AN: 1096387 Hom.: 171518 Cov.: 36 AF XY: 0.662 AC XY: 239866 AN XY: 362221

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.706

Gnomad4 OTH exome AF: 0.659

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.650 AC: 71065 AN: 109385 Hom.: 16929 Cov.: 21 AF XY: 0.631 AC XY: 19972 AN XY: 31661

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.650

Alfa AF: 0.690 Hom.: 81721

Bravo AF: 0.651

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 16, 2015	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Brunner syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.48

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: rs1137070; hg19: chrX-43603391; COSMIC: COSV58641635;