Genetic Variant NM_000240.4:c.118T>G (chrX-43683557-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000240.4(MAOA):c.118T>G(p.Leu40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. L40F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Consequence

MAOA
NM_000240.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Publications

0 publications found

Variant links:

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

MAOA links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15637434).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAOA	NM_000240.4	MANE Select	c.118T>G	p.Leu40Val	missense	Exon 2 of 15	NP_000231.1	Q53YE7
MAOA	NM_001270458.2		c.-282T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 16	NP_001257387.1	P21397-2
MAOA	NM_001270458.2		c.-282T>G		5_prime_UTR	Exon 3 of 16	NP_001257387.1	P21397-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAOA	ENST00000338702.4	TSL:1 MANE Select	c.118T>G	p.Leu40Val	missense	Exon 2 of 15	ENSP00000340684.3	P21397-1
MAOA	ENST00000542639.6	TSL:2	c.-282T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 16	ENSP00000440846.1	P21397-2
MAOA	ENST00000688006.1		c.-282T>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000510311.1	P21397-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.2

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.40

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.018

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.81

PhyloP100

2.2

PrimateAI

Benign

0.45

PROVEAN

Benign

0.11

REVEL

Benign

0.041

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.23

MutPred

0.46

Gain of MoRF binding (P = 0.2414)

MVP

0.32

MPC

0.68

ClinPred

0.067

GERP RS

2.9

Varity_R

0.28

gMVP

0.88

Mutation Taster

=68/32

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over