3-193648150-T-G

Variant names:

• chr3-193648150-T-G
• rs9831772
• NM_130837.3:c.1935+16T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130837.3(OPA1):​c.1935+16T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 1,569,684 control chromosomes in the GnomAD database, including 5,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (514 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4779 hom.)
• Consequence: OPA1 NM_130837.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.892
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant optic atrophy, classic form

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• optic atrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• OPA1-related optic atrophy with or without extraocular features

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• Behr syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type)

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• autosomal dominant optic atrophy plus syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000306963 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-193648150-T-G is Benign according to our data. Variant chr3-193648150-T-G is described in ClinVar as Benign. ClinVar VariationId is 95714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPA1	NM_130837.3	c.1935+16T>G		intron_variant	Intron 20 of 30	ENST00000361510.8	NP_570850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8	c.1935+16T>G		intron_variant	Intron 20 of 30	5	NM_130837.3	ENSP00000355324.2

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11809 AN: 152136 Hom.: 512 Cov.: 32

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0785

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.0921

GnomAD2 exomes AF: 0.0891 AC: 22354 AN: 250910 AF XY: 0.0877

Gnomad AFR exome AF: 0.0466

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.0793

Gnomad EAS exome AF: 0.0760

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.0778

Gnomad OTH exome AF: 0.0816

GnomAD4 exome AF: 0.0789 AC: 111883 AN: 1417428 Hom.: 4779 Cov.: 24 AF XY: 0.0793 AC XY: 56113 AN XY: 707986

African (AFR) AF: 0.0449 AC: 1460 AN: 32530

American (AMR) AF: 0.139 AC: 6222 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.0763 AC: 1970 AN: 25824

East Asian (EAS) AF: 0.0661 AC: 2606 AN: 39416

South Asian (SAS) AF: 0.0969 AC: 8269 AN: 85342

European-Finnish (FIN) AF: 0.101 AC: 5394 AN: 53356

Middle Eastern (MID) AF: 0.0621 AC: 353 AN: 5686

European-Non Finnish (NFE) AF: 0.0756 AC: 81066 AN: 1071742

Other (OTH) AF: 0.0771 AC: 4543 AN: 58908

GnomAD4 genome AF: 0.0776 AC: 11821 AN: 152256 Hom.: 514 Cov.: 32 AF XY: 0.0794 AC XY: 5909 AN XY: 74448

African (AFR) AF: 0.0483 AC: 2008 AN: 41546

American (AMR) AF: 0.130 AC: 1981 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0785 AC: 272 AN: 3464

East Asian (EAS) AF: 0.0720 AC: 373 AN: 5182

South Asian (SAS) AF: 0.100 AC: 483 AN: 4826

European-Finnish (FIN) AF: 0.106 AC: 1124 AN: 10608

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0778 AC: 5291 AN: 68034

Other (OTH) AF: 0.0969 AC: 204 AN: 2106

Alfa AF: 0.0774 Hom.: 291

Bravo AF: 0.0766

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Jul 07, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 05, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.52
PhyloP100		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9831772; hg19: chr3-193365939; COSMIC: COSV62479527; COSMIC: COSV62479527;