rs80356526

chr19-45553714-CCTCCTCCTTGTGGCGCTG-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_025136.4(OPA3):c.322_339del(p.Gln108_Glu113del) variant causes a 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. 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 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 4.97

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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. Variant chr19-45553714-CCTCCTCCTTGTGGCGCTG-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPA3	NM_025136.4	c.322_339del	p.Gln108_Glu113del	inframe_deletion	2/2	ENST00000263275.5
OPA3	XM_006723403.5	c.163_180del	p.Gln55_Glu60del	inframe_deletion	3/3
OPA3	NM_001017989.3	c.143-24276_143-24259del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPA3	ENST00000263275.5	c.322_339del	p.Gln108_Glu113del	inframe_deletion	2/2	1	NM_025136.4	P1
OPA3	ENST00000323060.4	c.143-24276_143-24259del		intron_variant		1
OPA3	ENST00000544371.1	c.163_180del	p.Gln55_Glu60del	inframe_deletion	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457026 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 724996

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

3-Methylglutaconic aciduria type 3 Pathogenic:1 Other:1

not provided, no classification provided	literature only	GeneReviews	-	Found in an individual of Turkish-Kurdish origin with Costeff syndrome -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jul 01, 2002	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs80356526; hg19: chr19-46056972;