3-193692091-TGA-T

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_130837.3(OPA1):​c.3013_3014delGA​(p.Asp1005CysfsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

OPA1
NM_130837.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.30

Publications

2 publications found
Variant links:
Genes affected
OPA1 (HGNC:8140): (OPA1 mitochondrial dynamin like GTPase) The protein encoded by this gene is a nuclear-encoded mitochondrial protein with similarity to dynamin-related GTPases. The encoded protein localizes to the inner mitochondrial membrane and helps regulate mitochondrial stability and energy output. This protein also sequesters cytochrome c. Mutations in this gene have been associated with optic atrophy type 1, which is a dominantly inherited optic neuropathy resulting in progressive loss of visual acuity, leading in many cases to legal blindness. [provided by RefSeq, Aug 2017]
OPA1 Gene-Disease associations (from GenCC):
  • autosomal dominant optic atrophy, classic form
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
  • optic atrophy
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
  • optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
  • OPA1-related optic atrophy with or without extraocular features
    Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
  • Behr syndrome
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type)
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • Leigh syndrome
    Inheritance: AR Classification: MODERATE Submitted by: ClinGen
  • autosomal dominant optic atrophy plus syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 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 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-193692091-TGA-T is Pathogenic according to our data. Variant chr3-193692091-TGA-T is described in ClinVar as [Pathogenic]. Clinvar id is 5092.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPA1NM_130837.3 linkc.3013_3014delGA p.Asp1005CysfsTer4 frameshift_variant Exon 30 of 31 ENST00000361510.8 NP_570850.2 O60313-10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OPA1ENST00000361510.8 linkc.3013_3014delGA p.Asp1005CysfsTer4 frameshift_variant Exon 30 of 31 5 NM_130837.3 ENSP00000355324.2 O60313-10

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autosomal dominant optic atrophy classic form Pathogenic:1
Jan 01, 2007
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
7.3
Mutation Taster
=0/200
disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs879255513; hg19: chr3-193409880; API