dbSNP rs80356526: OPA3:p.Gln108_Glu113del (chr19-45553714-CCTCCTCCTTGTGGCGCTG-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM4PP5

The NM_025136.4(OPA3):c.322_339delCAGCGCCACAAGGAGGAG(p.Gln108_Glu113del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000000686 in 1,457,026 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OPA3
NM_025136.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 4.97

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

optic atrophy 3
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
3-methylglutaconic aciduria type 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae)

OPA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_025136.4.

PP5

Variant 19-45553714-CCTCCTCCTTGTGGCGCTG-C is Pathogenic according to our data. Variant chr19-45553714-CCTCCTCCTTGTGGCGCTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 4242.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPA3	NM_025136.4 link	c.322_339delCAGCGCCACAAGGAGGAG	p.Gln108_Glu113del	conservative_inframe_deletion	Exon 2 of 2	ENST00000263275.5	NP_079412.1	Q9H6K4-1
OPA3	XM_006723403.5 link	c.163_180delCAGCGCCACAAGGAGGAG	p.Gln55_Glu60del	conservative_inframe_deletion	Exon 3 of 3		XP_006723466.1	B4DK77
OPA3	NM_001017989.3 link	c.143-24276_143-24259delCAGCGCCACAAGGAGGAG		intron_variant	Intron 1 of 1		NP_001017989.2	Q9H6K4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OPA3	ENST00000263275.5 link	c.322_339delCAGCGCCACAAGGAGGAG	p.Gln108_Glu113del	conservative_inframe_deletion	Exon 2 of 2	1	NM_025136.4	ENSP00000263275.4	Q9H6K4-1
OPA3	ENST00000323060.4 link	c.143-24276_143-24259delCAGCGCCACAAGGAGGAG		intron_variant	Intron 1 of 1	1		ENSP00000319817.3	Q9H6K4-2
OPA3	ENST00000544371.1 link	c.163_180delCAGCGCCACAAGGAGGAG	p.Gln55_Glu60del	conservative_inframe_deletion	Exon 2 of 2	2		ENSP00000442839.1	B4DK77

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457026

Hom.:

AF XY:

0.00

AC XY:

AN XY:

724996

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111350

Other (OTH)

AF:

0.00

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

3-Methylglutaconic aciduria type 3

Pathogenic:1Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

Found in an individual of Turkish-Kurdish origin with Costeff syndrome -

Jul 01, 2002

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.0

Mutation Taster

=30/170

disease causing (ClinVar)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over