rs780492515
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_025136.4(OPA3):c.487C>T(p.Leu163Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L163L) has been classified as Likely benign.
Frequency
Consequence
NM_025136.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPA3 | NM_025136.4 | c.487C>T | p.Leu163Phe | missense_variant | 2/2 | ENST00000263275.5 | |
OPA3 | XM_006723403.5 | c.328C>T | p.Leu110Phe | missense_variant | 3/3 | ||
OPA3 | NM_001017989.3 | c.143-24111C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPA3 | ENST00000263275.5 | c.487C>T | p.Leu163Phe | missense_variant | 2/2 | 1 | NM_025136.4 | P1 | |
OPA3 | ENST00000323060.4 | c.143-24111C>T | intron_variant | 1 | |||||
OPA3 | ENST00000544371.1 | c.328C>T | p.Leu110Phe | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000814 AC: 2AN: 245650Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134166
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460802Hom.: 0 Cov.: 62 AF XY: 0.00000413 AC XY: 3AN XY: 726812
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
3-Methylglutaconic aciduria type 3;C1833809:Optic atrophy 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 556177). This variant has not been reported in the literature in individuals affected with OPA3-related conditions. This variant is present in population databases (rs780492515, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 163 of the OPA3 protein (p.Leu163Phe). - |
3-Methylglutaconic aciduria type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 16, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at