9-129813557-AC-A

Position:

• chr9-129813557-AC-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TOR1A	NM_000113.3	c.*414delG		3_prime_UTR_variant	5/5	ENST00000351698.5	NP_000104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOR1A	ENST00000351698	c.*414delG		3_prime_UTR_variant	5/5	1	NM_000113.3	ENSP00000345719.4
TOR1A	ENST00000651202.1	c.*681delG		3_prime_UTR_variant	6/6			ENSP00000498222.1
TOR1A	ENST00000474192.1	n.*50delG		downstream_gene_variant		3

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

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0906

Gnomad4 ASJ exome AF: 0.0902

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.0438

Gnomad4 FIN exome AF: 0.0821

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0969

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

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.0866

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.137

Asia WGS AF: 0.102 AC: 353 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early-onset generalized limb-onset dystonia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35153737; hg19: chr9-132575836; COSMIC: COSV52213047; COSMIC: COSV52213047;