rs8111589

Variant names:

• chr19-45531300-C-T
• rs8111589
• ENST00000323060.4:c.143-1844G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017989.3(OPA3):​c.143-1844G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,846 control chromosomes in the GnomAD database, including 20,519 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (20519 hom., cov: 31)
• Consequence: OPA3 NM_001017989.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 23 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

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.143-1844G>A		intron	N/A	NP_001017989.2	Q9H6K4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPA3	ENST00000323060.4	TSL:1	c.143-1844G>A		intron	N/A	ENSP00000319817.3	Q9H6K4-2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78557 AN: 151728 Hom.: 20514 Cov.: 31

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.520

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.518 AC: 78596 AN: 151846 Hom.: 20519 Cov.: 31 AF XY: 0.513 AC XY: 38069 AN XY: 74202

African (AFR) AF: 0.469 AC: 19429 AN: 41408

American (AMR) AF: 0.461 AC: 7032 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2060 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2230 AN: 5172

South Asian (SAS) AF: 0.525 AC: 2527 AN: 4816

European-Finnish (FIN) AF: 0.507 AC: 5333 AN: 10516

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38272 AN: 67910

Other (OTH) AF: 0.514 AC: 1085 AN: 2110

Alfa AF: 0.550 Hom.: 68263

Bravo AF: 0.508

Asia WGS AF: 0.447 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.61
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs8111589;

hg19: chr19-46034558;