9-129814233-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000113.3(TOR1A):c.749-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,614,012 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 36 hom., cov: 32)

Exomes 𝑓: 0.017 ( 465 hom. )

Consequence

TOR1A
NM_000113.3 intron

Scores

Splicing: ADA: 0.0001530

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.587

Publications

1 publications found

Variant links:

Genes affected

TOR1A (HGNC:3098): (torsin family 1 member A) The protein encoded by this gene is a member of the AAA family of adenosine triphosphatases (ATPases), is related to the Clp protease/heat shock family and is expressed prominently in the substantia nigra pars compacta. Mutations in this gene result in the autosomal dominant disorder, torsion dystonia 1. [provided by RefSeq, Jul 2008]

TOR1A Gene-Disease associations (from GenCC):

early-onset generalized limb-onset dystonia
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Illumina, Orphanet
arthrogryposis multiplex congenita 5
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

TOR1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 9-129814233-G-T is Benign according to our data. Variant chr9-129814233-G-T is described in ClinVar as [Benign]. Clinvar id is 255137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1A	NM_000113.3 link	c.749-11C>A		intron_variant	Intron 4 of 4	ENST00000351698.5	NP_000104.1	O14656-1B3KPA1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TOR1A	ENST00000351698.5 link	c.749-11C>A	intron_variant	Intron 4 of 4	1	NM_000113.3	ENSP00000345719.4	O14656-1
TOR1A	ENST00000651202.1 link	c.*17-11C>A	intron_variant	Intron 5 of 5			ENSP00000498222.1	A0A494BZT7
TOR1A	ENST00000474192.1 link	n.333-11C>A	intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2024

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00413

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0695

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0609

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.0173

GnomAD2 exomes

AF:

0.0206

AC:

5169

AN:

251308

AF XY:

0.0237

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.0608

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00301

Gnomad NFE exome

AF:

0.0162

Gnomad OTH exome

AF:

0.0207

GnomAD4 exome

AF:

0.0168

AC:

24505

AN:

1461816

Hom.:

465

Cov.:

AF XY:

0.0185

AC XY:

13426

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00394

AC:

132

AN:

33480

American (AMR)

AF:

0.0133

AC:

593

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

1566

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0673

AC:

5803

AN:

86252

European-Finnish (FIN)

AF:

0.00326

AC:

174

AN:

53398

Middle Eastern (MID)

AF:

0.0583

AC:

335

AN:

5744

European-Non Finnish (NFE)

AF:

0.0133

AC:

14738

AN:

1111992

Other (OTH)

AF:

0.0192

AC:

1160

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1575

3150

4725

6300

7875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0133

AC:

2025

AN:

152196

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1045

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00426

AC:

177

AN:

41504

American (AMR)

AF:

0.0155

AC:

237

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0695

AC:

241

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0608

AC:

293

AN:

4822

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0147

AC:

1000

AN:

68002

Other (OTH)

AF:

0.0176

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

191

286

382

477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Dec 09, 2018

GeneDx

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

- -

Dystonic disorder

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Early-onset generalized limb-onset dystonia

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.6

(source)

DANN

Benign

0.80

PhyloP100

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.022

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

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9-129814233-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over