19-45528866-T-C

Position:

• chr19-45528866-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000323060.4(OPA3):​c.*190A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 614,348 control chromosomes in the GnomAD database, including 2,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (598 hom., cov: 31)
  • Exomes 𝑓: 0.096 (2323 hom.)
• Consequence: OPA3 ENST00000323060.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.95

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 19-45528866-T-C is Benign according to our data. Variant chr19-45528866-T-C is described in ClinVar as [Benign]. Clinvar id is 1263205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPA3	NM_001017989.3	c.*190A>G		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPA3	ENST00000323060.4	c.*190A>G		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12589 AN: 151380 Hom.: 596 Cov.: 31

Gnomad AFR AF: 0.0532

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.0793

GnomAD4 exome AF: 0.0959 AC: 44407 AN: 462850 Hom.: 2323 Cov.: 6 AF XY: 0.0978 AC XY: 23644 AN XY: 241712

Gnomad4 AFR exome AF: 0.0524

Gnomad4 AMR exome AF: 0.0535

Gnomad4 ASJ exome AF: 0.0972

Gnomad4 EAS exome AF: 0.0874

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0940

Gnomad4 OTH exome AF: 0.0952

GnomAD4 genome AF: 0.0831 AC: 12592 AN: 151498 Hom.: 598 Cov.: 31 AF XY: 0.0857 AC XY: 6343 AN XY: 74012

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0928

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.0632 Hom.: 87

Bravo AF: 0.0779

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.6
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73568948; hg19: chr19-46032124; COSMIC: COSV55606478; COSMIC: COSV55606478;