rs1183

Variant names:

• chr9-129813758-G-C
• rs1183
• NM_000113.3:c.*214C>G

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.*214C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 657,396 control chromosomes in the GnomAD database, including 2,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (588 hom., cov: 33)
  • Exomes 𝑓: 0.079 (1843 hom.)
• Consequence: TOR1A NM_000113.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.224
• Publications: 12 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=-0.82).
• BP6: Variant 9-129813758-G-C is Benign according to our data. Variant chr9-129813758-G-C is described in ClinVar as Benign. ClinVar VariationId is 365228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0886 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.*214C>G		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.*214C>G		3_prime_UTR	Exon 5 of 5	ENSP00000345719.4	O14656-1
	TOR1A	ENST00000651202.1		c.*481C>G		3_prime_UTR	Exon 6 of 6	ENSP00000498222.1	A0A494BZT7
	TOR1A	ENST00000474192.1	TSL:3	n.797C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12551 AN: 152206 Hom.: 586 Cov.: 33

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0903

GnomAD4 exome AF: 0.0794 AC: 40106 AN: 505072 Hom.: 1843 Cov.: 6 AF XY: 0.0801 AC XY: 21430 AN XY: 267620

African (AFR) AF: 0.0914 AC: 1292 AN: 14134

American (AMR) AF: 0.0603 AC: 1550 AN: 25710

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 1840 AN: 15276

East Asian (EAS) AF: 0.00205 AC: 64 AN: 31206

South Asian (SAS) AF: 0.0799 AC: 4019 AN: 50330

European-Finnish (FIN) AF: 0.0421 AC: 1271 AN: 30182

Middle Eastern (MID) AF: 0.122 AC: 259 AN: 2120

European-Non Finnish (NFE) AF: 0.0885 AC: 27271 AN: 308018

Other (OTH) AF: 0.0904 AC: 2540 AN: 28096

GnomAD4 genome AF: 0.0825 AC: 12561 AN: 152324 Hom.: 588 Cov.: 33 AF XY: 0.0789 AC XY: 5877 AN XY: 74488

African (AFR) AF: 0.0910 AC: 3782 AN: 41560

American (AMR) AF: 0.0812 AC: 1242 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5186

South Asian (SAS) AF: 0.0782 AC: 378 AN: 4832

European-Finnish (FIN) AF: 0.0400 AC: 425 AN: 10622

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0853 AC: 5800 AN: 68034

Other (OTH) AF: 0.0888 AC: 188 AN: 2116

Alfa AF: 0.0781 Hom.: 77

Bravo AF: 0.0856

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		0.22
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: rs1183; hg19: chr9-132576037;