9-129813557-AC-A

Variant names:

• chr9-129813557-AC-A
• rs35153737
• NM_000113.3:c.*414delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400
• Publications: 3 publications found

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

ACMG classification

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 VariationId 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.

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.*414delG		3_prime_UTR	Exon 5 of 5	NP_000104.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1A	ENST00000351698.5	TSL:1 MANE Select	c.*414delG		3_prime_UTR	Exon 5 of 5	ENSP00000345719.4
	TOR1A	ENST00000651202.1		c.*681delG		3_prime_UTR	Exon 6 of 6	ENSP00000498222.1
	TOR1A	ENST00000474192.1	TSL:3	n.*50delG		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21014 AN: 149228 Hom.: 1599 Cov.: 32

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.: 0 AF XY: 0.0869 AC XY: 6818 AN XY: 78440

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: 64 AN: 526

European-Non Finnish (NFE) AF: 0.106 AC: 8944 AN: 84684

Other (OTH) AF: 0.0969 AC: 676 AN: 6978

GnomAD4 genome AF: 0.141 AC: 21017 AN: 149344 Hom.: 1596 Cov.: 32 AF XY: 0.136 AC XY: 9920 AN XY: 73026

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: 43 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8586 AN: 67366

Other (OTH) AF: 0.137 AC: 287 AN: 2092

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.102 AC: 353 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Early-onset generalized limb-onset dystonia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0040
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: rs35153737; hg19: chr9-132575836; COSMIC: COSV52213047; COSMIC: COSV52213047;