chrX-43683557-T-G

Variant names:

• chrX-43683557-T-G
• rs1230848293
• NM_000240.4:c.118T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270458.2(MAOA):​c.-282T>G variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAOA NM_001270458.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15637434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.118T>G	p.Leu40Val	missense_variant	Exon 2 of 15	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.-282T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 16		NP_001257387.1
MAOA	NM_001270458.2	c.-282T>G		5_prime_UTR_variant	Exon 3 of 16		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.118T>G	p.Leu40Val	missense_variant	Exon 2 of 15	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jul 16, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.11
DEOGEN2	Benign	0.40	T
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.81	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.46		Gain of MoRF binding (P = 0.2414);
MVP		0.32
MPC		0.68
ClinPred		0.067	T
GERP RS		2.9
Varity_R		0.28
gMVP		0.88

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: rs1230848293; hg19: chrX-43542805;