dbSNP rs3842225: TOR1A:c.*824delG (chr9-129813147-GC-G) – 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.*824delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,248 control chromosomes in the GnomAD database, including 2,569 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2568 hom., cov: 29)

Exomes 𝑓: 0.14 ( 1 hom. )

Consequence

TOR1A
NM_000113.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.189

Publications

12 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: PanelApp Australia, Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
arthrogryposis multiplex congenita 5
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), 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 9-129813147-GC-G is Benign according to our data. Variant chr9-129813147-GC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 365216.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000113.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1A	NM_000113.3	MANE Select	c.*824delG		3_prime_UTR	Exon 5 of 5	NP_000104.1	O14656-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1A	ENST00000351698.5	TSL:1 MANE Select	c.*824delG		3_prime_UTR	Exon 5 of 5	ENSP00000345719.4	O14656-1
	TOR1A	ENST00000651202.1		c.*1091delG		3_prime_UTR	Exon 6 of 6	ENSP00000498222.1	A0A494BZT7

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25165

AN:

152074

Hom.:

2569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0399

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.188

GnomAD4 exome

AF:

0.143

AC:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.130

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.165

AC:

25164

AN:

152192

Hom.:

2568

Cov.:

AF XY:

0.168

AC XY:

12475

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0398

AC:

1654

AN:

41544

American (AMR)

AF:

0.182

AC:

2785

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

683

AN:

3470

East Asian (EAS)

AF:

0.201

AC:

1039

AN:

5174

South Asian (SAS)

AF:

0.189

AC:

910

AN:

4826

European-Finnish (FIN)

AF:

0.246

AC:

2612

AN:

10598

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14864

AN:

67994

Other (OTH)

AF:

0.191

AC:

404

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1037

2074

3112

4149

5186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0977

Hom.:

167

Bravo

AF:

0.153

Asia WGS

AF:

0.221

AC:

764

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Early-onset generalized limb-onset dystonia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.19

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over