Variant rs1022155897 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1

The ENST00000263275.5(OPA3):c.367C>T(p.Arg123Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000894 in 1,453,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R123P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

OPA3
ENST00000263275.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a chain Optic atrophy 3 protein (size 177) in uniprot entity OPA3_HUMAN there are 11 pathogenic changes around while only 4 benign (73%) in ENST00000263275.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OPA3	NM_025136.4 linkuse as main transcript	c.367C>T	p.Arg123Trp	missense_variant	2/2	ENST00000263275.5	NP_079412.1
OPA3	XM_006723403.5 linkuse as main transcript	c.208C>T	p.Arg70Trp	missense_variant	3/3		XP_006723466.1
OPA3	NM_001017989.3 linkuse as main transcript	c.143-24231C>T		intron_variant			NP_001017989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPA3	ENST00000263275.5 linkuse as main transcript	c.367C>T	p.Arg123Trp	missense_variant	2/2	1	NM_025136.4	ENSP00000263275	P1	Q9H6K4-1
OPA3	ENST00000323060.4 linkuse as main transcript	c.143-24231C>T		intron_variant		1		ENSP00000319817		Q9H6K4-2
OPA3	ENST00000544371.1 linkuse as main transcript	c.208C>T	p.Arg70Trp	missense_variant	2/2	2		ENSP00000442839

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000868

AC:

AN:

230418

Hom.:

AF XY:

0.00000787

AC XY:

AN XY:

127036

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:

0.00000970

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.00000894

AC:

AN:

1453360

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723146

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000319

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

3-Methylglutaconic aciduria type 3

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Apr 14, 2020

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.80

D;D

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

D;D

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;N;N

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

1.0

D;.

Vest4

0.10

MutPred

0.56

Loss of disorder (P = 0.0107);.;

MVP

0.87

ClinPred

0.78

GERP RS

4.6

Varity_R

0.56

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