chr9-129813781-C-A

Variant names:

• chr9-129813781-C-A
• rs1182
• NM_000113.3:c.*191G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000113.3(TOR1A):​c.*191G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 797,746 control chromosomes in the GnomAD database, including 17,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2593 hom., cov: 32)
  • Exomes 𝑓: 0.21 (14695 hom.)
• Consequence: TOR1A NM_000113.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.16
• Publications: 38 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: 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-129813781-C-A is Benign according to our data. Variant chr9-129813781-C-A is described in ClinVar as Benign. ClinVar VariationId is 365229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.*191G>T		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.*191G>T		3_prime_UTR	Exon 5 of 5	ENSP00000345719.4	O14656-1
	TOR1A	ENST00000651202.1		c.*458G>T		3_prime_UTR	Exon 6 of 6	ENSP00000498222.1	A0A494BZT7
	TOR1A	ENST00000474192.1	TSL:3	n.774G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25569 AN: 152078 Hom.: 2594 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.208 AC: 134565 AN: 645550 Hom.: 14695 Cov.: 9 AF XY: 0.208 AC XY: 70179 AN XY: 337912

African (AFR) AF: 0.0483 AC: 842 AN: 17446

American (AMR) AF: 0.165 AC: 5258 AN: 31896

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 3647 AN: 17686

East Asian (EAS) AF: 0.238 AC: 7654 AN: 32176

South Asian (SAS) AF: 0.186 AC: 10741 AN: 57596

European-Finnish (FIN) AF: 0.233 AC: 7524 AN: 32258

Middle Eastern (MID) AF: 0.181 AC: 461 AN: 2554

European-Non Finnish (NFE) AF: 0.218 AC: 91574 AN: 420712

Other (OTH) AF: 0.207 AC: 6864 AN: 33226

GnomAD4 genome AF: 0.168 AC: 25568 AN: 152196 Hom.: 2593 Cov.: 32 AF XY: 0.170 AC XY: 12669 AN XY: 74408

African (AFR) AF: 0.0490 AC: 2035 AN: 41552

American (AMR) AF: 0.183 AC: 2797 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 685 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1034 AN: 5160

South Asian (SAS) AF: 0.189 AC: 911 AN: 4824

European-Finnish (FIN) AF: 0.247 AC: 2619 AN: 10590

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14867 AN: 67988

Other (OTH) AF: 0.192 AC: 407 AN: 2116

Alfa AF: 0.199 Hom.: 714

Bravo AF: 0.157

Asia WGS AF: 0.220 AC: 763 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dystonic disorder (1)
-	-	1	Early-onset generalized limb-onset dystonia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.46
DANN	Benign	0.67
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1182; hg19: chr9-132576060;