3-193614631-C-CTGTG

Position:

• chr3-193614631-C-CTGTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_130837.3(OPA1):​c.33-90_33-87dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 895,146 control chromosomes in the GnomAD database, including 80,882 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14086 hom., cov: 0)
  • Exomes 𝑓: 0.42 (66796 hom.)
• Consequence: OPA1 NM_130837.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.634

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-193614631-C-CTGTG is Benign according to our data. Variant chr3-193614631-C-CTGTG is described in ClinVar as [Benign]. Clinvar id is 1275115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA1	NM_130837.3	c.33-90_33-87dup		intron_variant		ENST00000361510.8	NP_570850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8	c.33-90_33-87dup		intron_variant		5	NM_130837.3	ENSP00000355324	A1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64836 AN: 151438 Hom.: 14075 Cov.: 0

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.417 AC: 310398 AN: 743592 Hom.: 66796 AF XY: 0.415 AC XY: 164983 AN XY: 397676

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.428 AC: 64889 AN: 151554 Hom.: 14086 Cov.: 0 AF XY: 0.430 AC XY: 31779 AN XY: 73986

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.417

Alfa AF: 0.444 Hom.: 1596

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58340380; hg19: chr3-193332420;