chr19-45529253-G-G

Variant names:

• chr19-45529253-G-G
• ENST00000323060.4:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001017989.3(OPA3):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: OPA3 NM_001017989.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017989.3. 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_001017989.3		c.		exon_region	Exon 2 of 2	NP_001017989.2	Q9H6K4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPA3	ENST00000323060.4	TSL:1	c.		exon_region	Exon 2 of 2	ENSP00000319817.3	Q9H6K4-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.021

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.

Other links and lift over

hg19: chr19-46032511;