NM_025136.4:c.367C>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_025136.4(OPA3):c.367C>A(p.Arg123Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000688 in 1,453,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
OPA3
NM_025136.4 synonymous
NM_025136.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 6.00
Publications
0 publications found
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]
OPA3 Gene-Disease associations (from GenCC):
- optic atrophy 3Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
- 3-methylglutaconic aciduria type 3Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 19-45553687-G-T is Benign according to our data. Variant chr19-45553687-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 462147.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_025136.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| OPA3 | NM_025136.4 | MANE Select | c.367C>A | p.Arg123Arg | synonymous | Exon 2 of 2 | NP_079412.1 | ||
| OPA3 | NM_001017989.3 | c.143-24231C>A | intron | N/A | NP_001017989.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| OPA3 | ENST00000263275.5 | TSL:1 MANE Select | c.367C>A | p.Arg123Arg | synonymous | Exon 2 of 2 | ENSP00000263275.4 | ||
| OPA3 | ENST00000323060.4 | TSL:1 | c.143-24231C>A | intron | N/A | ENSP00000319817.3 | |||
| OPA3 | ENST00000544371.1 | TSL:2 | c.208C>A | p.Arg70Arg | synonymous | Exon 2 of 2 | ENSP00000442839.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453358Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0AN XY: 723144 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1453358
Hom.:
Cov.:
61
AF XY:
AC XY:
0
AN XY:
723144
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33404
American (AMR)
AF:
AC:
0
AN:
44318
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26036
East Asian (EAS)
AF:
AC:
0
AN:
39610
South Asian (SAS)
AF:
AC:
0
AN:
86090
European-Finnish (FIN)
AF:
AC:
0
AN:
47388
Middle Eastern (MID)
AF:
AC:
0
AN:
5740
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1110598
Other (OTH)
AF:
AC:
0
AN:
60174
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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8
10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
3-Methylglutaconic aciduria type 3;C1833809:Optic atrophy 3 Benign:1
Apr 25, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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