rs1555736803
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_025136.4(OPA3):c.100_101insA(p.Ser34LysfsTer45) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
OPA3
NM_025136.4 frameshift
NM_025136.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.43
Genes affected
OPA3 (HGNC:8142): (outer mitochondrial membrane lipid metabolism regulator OPA3) The mouse ortholog of this protein co-purifies with the mitochondrial inner membrane. Mutations in this gene have been shown to result in 3-methylglutaconic aciduria type III and autosomal dominant optic atrophy and cataract. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 17 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-45584664-C-CT is Pathogenic according to our data. Variant chr19-45584664-C-CT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 557484.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPA3 | NM_025136.4 | c.100_101insA | p.Ser34LysfsTer45 | frameshift_variant | 1/2 | ENST00000263275.5 | |
OPA3 | NM_001017989.3 | c.100_101insA | p.Ser34LysfsTer199 | frameshift_variant | 1/2 | ||
OPA3 | XM_006723403.5 | c.-200_-199insA | 5_prime_UTR_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPA3 | ENST00000263275.5 | c.100_101insA | p.Ser34LysfsTer45 | frameshift_variant | 1/2 | 1 | NM_025136.4 | P1 | |
OPA3 | ENST00000323060.4 | c.100_101insA | p.Ser34LysfsTer199 | frameshift_variant | 1/2 | 1 | |||
OPA3 | ENST00000544371.1 | c.-18+17430_-18+17431insA | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
3-Methylglutaconic aciduria type 3 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 29, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at