3-193618850-T-C

Position:

• chr3-193618850-T-C

Variant summary

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

The NM_130837.3(OPA1):​c.611-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,593,068 control chromosomes in the GnomAD database, including 149,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14298 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134840 hom.)
• Consequence: OPA1 NM_130837.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.02

Genes affected

OPA1 (HGNC:8140): (OPA1 mitochondrial dynamin like GTPase) The protein encoded by this gene is a nuclear-encoded mitochondrial protein with similarity to dynamin-related GTPases. The encoded protein localizes to the inner mitochondrial membrane and helps regulate mitochondrial stability and energy output. This protein also sequesters cytochrome c. Mutations in this gene have been associated with optic atrophy type 1, which is a dominantly inherited optic neuropathy resulting in progressive loss of visual acuity, leading in many cases to legal blindness. [provided by RefSeq, Aug 2017]

OPA1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-193618850-T-C is Benign according to our data. Variant chr3-193618850-T-C is described in ClinVar as [Benign]. Clinvar id is 95728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-193618850-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA1	NM_130837.3	c.611-19T>C		intron_variant		ENST00000361510.8	NP_570850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8	c.611-19T>C		intron_variant		5	NM_130837.3	ENSP00000355324.2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65259 AN: 151804 Hom.: 14285 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.415

GnomAD3 exomes AF: 0.425 AC: 106737 AN: 251250 Hom.: 23228 AF XY: 0.421 AC XY: 57202 AN XY: 135794

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.332

Gnomad SAS exome AF: 0.378

Gnomad FIN exome AF: 0.547

Gnomad NFE exome AF: 0.437

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.429 AC: 618431 AN: 1441146 Hom.: 134840 Cov.: 28 AF XY: 0.427 AC XY: 306556 AN XY: 718102

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.428

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.430 AC: 65315 AN: 151922 Hom.: 14298 Cov.: 32 AF XY: 0.432 AC XY: 32057 AN XY: 74258

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.417

Alfa AF: 0.392 Hom.: 3209

Bravo AF: 0.423

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 01, 2011	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 23, 2015	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3772393; hg19: chr3-193336639; COSMIC: COSV62479005;