rs3842225

Positions:

• chr9-129813147-GC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000351698.5(TOR1A):​c.*824del 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 ENST00000351698.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.189

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 9-129813147-GC-G is Benign according to our data. Variant chr9-129813147-GC-G is described in ClinVar as [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOR1A	NM_000113.3	c.*824del		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	ENST00000351698.5	c.*824del		3_prime_UTR_variant	5/5	1	NM_000113.3	ENSP00000345719	P1
TOR1A	ENST00000651202.1	c.*1091del		3_prime_UTR_variant	6/6			ENSP00000498222

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25165 AN: 152074 Hom.: 2569 Cov.: 29

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: 8 AN: 56 Hom.: 1 Cov.: 0 AF XY: 0.143 AC XY: 4 AN XY: 28

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.165 AC: 25164 AN: 152192 Hom.: 2568 Cov.: 29 AF XY: 0.168 AC XY: 12475 AN XY: 74402

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.191

Alfa AF: 0.0977 Hom.: 167

Bravo AF: 0.153

Asia WGS AF: 0.221 AC: 764 AN: 3478

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: rs3842225; hg19: chr9-132575426; COSMIC: COSV52213041; COSMIC: COSV52213041;