Variant rs1382779104 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_025136.4(OPA3):c.214A>G(p.Asn72Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

OPA3
NM_025136.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.86

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]

OPA3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.941

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA3	NM_025136.4 linkuse as main transcript	c.214A>G	p.Asn72Asp	missense_variant	2/2	ENST00000263275.5	NP_079412.1	Q9H6K4-1
OPA3	XM_006723403.5 linkuse as main transcript	c.55A>G	p.Asn19Asp	missense_variant	3/3		XP_006723466.1	B4DK77
OPA3	NM_001017989.3 linkuse as main transcript	c.143-24384A>G		intron_variant			NP_001017989.2	Q9H6K4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OPA3	ENST00000263275.5 linkuse as main transcript	c.214A>G	p.Asn72Asp	missense_variant	2/2	1	NM_025136.4	ENSP00000263275.4	Q9H6K4-1
OPA3	ENST00000323060.4 linkuse as main transcript	c.143-24384A>G		intron_variant		1		ENSP00000319817.3	Q9H6K4-2
OPA3	ENST00000544371.1 linkuse as main transcript	c.55A>G	p.Asn19Asp	missense_variant	2/2	2		ENSP00000442839.1	B4DK77

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000811

AC:

AN:

246722

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134480

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000897

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460716

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000720

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.000223

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

May 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

D;D

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

T;T

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Uncertain

0.48

MutationAssessor

Uncertain

2.5

M;.

PROVEAN

Uncertain

-4.2

D;D

REVEL

Pathogenic

0.79

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

D;.

Vest4

0.68

MutPred

0.81

Loss of methylation at K69 (P = 0.0827);.;

MVP

0.78

ClinPred

0.74

GERP RS

4.8

Varity_R

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over