rs780647851
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_000240.4(MAOA):c.890G>A(p.Arg297Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,205,528 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R297R) has been classified as Benign.
Frequency
Consequence
NM_000240.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAOA | NM_000240.4 | c.890G>A | p.Arg297Gln | missense_variant | 8/15 | ENST00000338702.4 | |
MAOA | NM_001270458.2 | c.491G>A | p.Arg164Gln | missense_variant | 9/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAOA | ENST00000338702.4 | c.890G>A | p.Arg297Gln | missense_variant | 8/15 | 1 | NM_000240.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000180 AC: 2AN: 111380Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33550
GnomAD3 exomes AF: 0.0000164 AC: 3AN: 183152Hom.: 0 AF XY: 0.0000443 AC XY: 3AN XY: 67730
GnomAD4 exome AF: 0.0000320 AC: 35AN: 1094148Hom.: 0 Cov.: 30 AF XY: 0.0000389 AC XY: 14AN XY: 359604
GnomAD4 genome ? AF: 0.0000180 AC: 2AN: 111380Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33550
ClinVar
Submissions by phenotype
Brunner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces arginine with glutamine at codon 297 of the MAOA protein (p.Arg297Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs780647851, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with MAOA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at