Genetic Variant NM_130837.3:c.1035+32T>C (chr3-193637313-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_130837.3(OPA1):c.1035+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,412,594 control chromosomes in the GnomAD database, including 131,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14101 hom., cov: 30)

Exomes 𝑓: 0.43 ( 117440 hom. )

Consequence

OPA1
NM_130837.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0240

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 3-193637313-T-C is Benign according to our data. Variant chr3-193637313-T-C is described in ClinVar as [Benign]. Clinvar id is 95730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-193637313-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 rank	MANE	Protein	UniProt
OPA1	NM_130837.3 link	c.1035+32T>C		intron_variant	Intron 10 of 30	ENST00000361510.8	NP_570850.2	O60313-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8 link	c.1035+32T>C		intron_variant	Intron 10 of 30	5	NM_130837.3	ENSP00000355324.2		O60313-10

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64673

AN:

151178

Hom.:

14087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.541

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.424

AC:

105597

AN:

249148

Hom.:

22936

AF XY:

0.420

AC XY:

56580

AN XY:

134668

show subpopulations

Gnomad AFR exome

AF:

0.416

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.332

Gnomad SAS exome

AF:

0.376

Gnomad FIN exome

AF:

0.546

Gnomad NFE exome

AF:

0.437

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.428

AC:

539842

AN:

1261294

Hom.:

117440

Cov.:

AF XY:

0.426

AC XY:

271417

AN XY:

637656

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.400

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.377

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.434

Gnomad4 OTH exome

AF:

0.421

GnomAD4 genome

AF:

0.428

AC:

64731

AN:

151300

Hom.:

14101

Cov.:

AF XY:

0.430

AC XY:

31745

AN XY:

73878

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.541

Gnomad4 NFE

AF:

0.435

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.429

Hom.:

2629

Bravo

AF:

0.420

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19581274, 11810296) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Feb 22, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.87

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over