19-45529145-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_001017989.3(OPA3):ā€‹c.454C>Gā€‹(p.Leu152Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,457,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

OPA3
NM_001017989.3 missense

Scores

2
7
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.46
Variant links:
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 Uncertain_significance. Variant got 3 ACMG points.

PM1
In a chain Optic atrophy 3 protein (size 177) in uniprot entity OPA3_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_001017989.3
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41224355).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPA3NM_001017989.3 linkc.454C>G p.Leu152Val missense_variant Exon 2 of 2 NP_001017989.2 Q9H6K4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OPA3ENST00000323060.4 linkc.454C>G p.Leu152Val missense_variant Exon 2 of 2 1 ENSP00000319817.3 Q9H6K4-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000422
AC:
1
AN:
236892
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
130248
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1457198
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
724876
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000896
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756
ExAC
AF:
0.00000832
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.033
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
22
DANN
Uncertain
1.0
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.78
T
M_CAP
Pathogenic
0.65
D
MetaRNN
Benign
0.41
T
MetaSVM
Uncertain
0.41
D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.37
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.14
T
Polyphen
1.0
D
Vest4
0.20
MutPred
0.10
Gain of MoRF binding (P = 0.2168);
MVP
0.73
MPC
0.94
ClinPred
0.98
D
GERP RS
3.4
gMVP
0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376630127; hg19: chr19-46032403; API