rs771740634
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000240.4(MAOA):c.402G>A(p.Met134Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000513 in 1,168,470 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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. M134V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000240.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAOA | NM_000240.4 | c.402G>A | p.Met134Ile | missense_variant | 4/15 | ENST00000338702.4 | |
MAOA | NM_001270458.2 | c.3G>A | p.Met1? | start_lost | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAOA | ENST00000338702.4 | c.402G>A | p.Met134Ile | missense_variant | 4/15 | 1 | NM_000240.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111573Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33757
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183090Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67628
GnomAD4 exome AF: 0.00000378 AC: 4AN: 1056897Hom.: 0 Cov.: 26 AF XY: 0.00000613 AC XY: 2AN XY: 326109
GnomAD4 genome ? AF: 0.0000179 AC: 2AN: 111573Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33757
ClinVar
Submissions by phenotype
Brunner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2018 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MAOA-related disease. This variant is present in population databases (rs771740634, ExAC 0.004%). This sequence change replaces methionine with isoleucine at codon 134 of the MAOA protein (p.Met134Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at