rs8111589

Positions:

• chr19-45531300-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000323060.4(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 ENST00000323060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA3	NM_001017989.3	c.143-1844G>A		intron_variant			NP_001017989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPA3	ENST00000323060.4	c.143-1844G>A		intron_variant		1		ENSP00000319817

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

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.514

Alfa AF: 0.558 Hom.: 51711

Bravo AF: 0.508

Asia WGS AF: 0.447 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8111589; hg19: chr19-46034558;