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, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
3-methylglutaconic aciduria type 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women's Health, G2P

OPA3 links:

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new If you want to explore the variant's impact on the transcript NM_025136.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 VariationId is 4242.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025136.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPA3	NM_025136.4	MANE Select	c.322_339delCAGCGCCACAAGGAGGAG	p.Gln108_Glu113del	conservative_inframe_deletion	Exon 2 of 2	NP_079412.1	Q9H6K4-1
	OPA3	NM_001017989.3		c.143-24276_143-24259delCAGCGCCACAAGGAGGAG		intron	N/A	NP_001017989.2	Q9H6K4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OPA3	ENST00000263275.5	TSL:1 MANE Select	c.322_339delCAGCGCCACAAGGAGGAG	p.Gln108_Glu113del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000263275.4	Q9H6K4-1
OPA3	ENST00000323060.4	TSL:1	c.143-24276_143-24259delCAGCGCCACAAGGAGGAG		intron	N/A	ENSP00000319817.3	Q9H6K4-2
OPA3	ENST00000544371.1	TSL:2	c.163_180delCAGCGCCACAAGGAGGAG	p.Gln55_Glu60del	conservative_inframe_deletion	Exon 2 of 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

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

3-Methylglutaconic aciduria type 3 (2)

Computational scores

Source: dbNSFP v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over