rs201519600
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_000240.4(MAOA):āc.137A>Gā(p.Asp46Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000168 in 1,206,525 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 65 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000240.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000537 AC: 6AN: 111680Hom.: 0 Cov.: 22 AF XY: 0.0000591 AC XY: 2AN XY: 33844
GnomAD3 exomes AF: 0.0000491 AC: 9AN: 183292Hom.: 0 AF XY: 0.0000590 AC XY: 4AN XY: 67814
GnomAD4 exome AF: 0.000180 AC: 197AN: 1094845Hom.: 0 Cov.: 28 AF XY: 0.000175 AC XY: 63AN XY: 360291
GnomAD4 genome AF: 0.0000537 AC: 6AN: 111680Hom.: 0 Cov.: 22 AF XY: 0.0000591 AC XY: 2AN XY: 33844
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.137A>G (p.D46G) alteration is located in exon 2 (coding exon 2) of the MAOA gene. This alteration results from a A to G substitution at nucleotide position 137, causing the aspartic acid (D) at amino acid position 46 to be replaced by a glycine (G). The heterozygous missense change is ultra rare in healthy individuals:_x000D_ Based on data from the NHLBI Exome Sequencing Project (ESP), the MAOA c.137A>G alteration was not observed among 6,503 individuals tested. Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project. This variant is reported in the SNPDatabase as rs201519600. The altered amino acid is conserved throughout evolution:_x000D_ The p.D46 amino acid is well conserved in available vertebrate species. The amino acid is located in a functionally important protein domain:_x000D_ The p.D46G amino acid is located within the FAD-binding domain of the MAOA protein (Colibus, 2005). In silico prediction is conflicting:_x000D_ The p.D46G alteration is predicted to be possibly damaging by Polyphen and tolerated by SIFT in silico analyses. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Brunner syndrome Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 46 of the MAOA protein (p.Asp46Gly). This variant is present in population databases (rs201519600, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MAOA-related conditions. ClinVar contains an entry for this variant (Variation ID: 225101). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MAOA protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at