Genetic Variant TOR1A:c.*414delG (chr9-129813557-AC-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000113.3(TOR1A):c.*414delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 293,888 control chromosomes in the GnomAD database, including 2,130 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1596 hom., cov: 32)

Exomes 𝑓: 0.093 ( 534 hom. )

Consequence

TOR1A
NM_000113.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00400

Publications

3 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 -10 ACMG points.

BP6

Variant 9-129813557-AC-A is Benign according to our data. Variant chr9-129813557-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 365224.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1A	NM_000113.3 link	c.*414delG		3_prime_UTR_variant	Exon 5 of 5	ENST00000351698.5	NP_000104.1	O14656-1B3KPA1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TOR1A	ENST00000351698.5 link	c.*414delG	3_prime_UTR_variant	Exon 5 of 5	1	NM_000113.3	ENSP00000345719.4	O14656-1
TOR1A	ENST00000651202.1 link	c.*681delG	3_prime_UTR_variant	Exon 6 of 6			ENSP00000498222.1	A0A494BZT7
TOR1A	ENST00000474192.1 link	n.*50delG	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21014

AN:

149228

Hom.:

1599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.0529

Gnomad FIN

AF:

0.0866

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.138

GnomAD4 exome

AF:

0.0930

AC:

13438

AN:

144544

Hom.:

534

Cov.:

AF XY:

0.0869

AC XY:

6818

AN XY:

78440

show subpopulations

African (AFR)

AF:

0.165

AC:

607

AN:

3680

American (AMR)

AF:

0.0906

AC:

434

AN:

4788

Ashkenazi Jewish (ASJ)

AF:

0.0902

AC:

306

AN:

3392

East Asian (EAS)

AF:

0.109

AC:

593

AN:

5442

South Asian (SAS)

AF:

0.0438

AC:

1218

AN:

27794

European-Finnish (FIN)

AF:

0.0821

AC:

596

AN:

7260

Middle Eastern (MID)

AF:

0.122

AC:

AN:

526

European-Non Finnish (NFE)

AF:

0.106

AC:

8944

AN:

84684

Other (OTH)

AF:

0.0969

AC:

676

AN:

6978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

508

1016

1525

2033

2541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.141

AC:

21017

AN:

149344

Hom.:

1596

Cov.:

AF XY:

0.136

AC XY:

9920

AN XY:

73026

show subpopulations

African (AFR)

AF:

0.203

AC:

8041

AN:

39622

American (AMR)

AF:

0.118

AC:

1781

AN:

15122

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

343

AN:

3414

East Asian (EAS)

AF:

0.138

AC:

709

AN:

5152

South Asian (SAS)

AF:

0.0526

AC:

253

AN:

4810

European-Finnish (FIN)

AF:

0.0866

AC:

915

AN:

10562

Middle Eastern (MID)

AF:

0.147

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.127

AC:

8586

AN:

67366

Other (OTH)

AF:

0.137

AC:

287

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

809

1617

2426

3234

4043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Asia WGS

AF:

0.102

AC:

353

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early-onset generalized limb-onset dystonia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0040

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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9-129813557-AC-A

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