rs1045441

Variant names:

• chr9-129813518-A-T
• rs1045441
• NM_000113.3:c.*454T>A

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.*454T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 278,610 control chromosomes in the GnomAD database, including 966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (589 hom., cov: 32)
  • Exomes 𝑓: 0.072 (377 hom.)
• Consequence: TOR1A NM_000113.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.129
• Publications: 7 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=-0.83).
• BP6: Variant 9-129813518-A-T is Benign according to our data. Variant chr9-129813518-A-T is described in ClinVar as Benign. ClinVar VariationId is 365220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0892 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.*454T>A		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.*454T>A		3_prime_UTR	Exon 5 of 5	ENSP00000345719.4	O14656-1
	TOR1A	ENST00000651202.1		c.*721T>A		3_prime_UTR	Exon 6 of 6	ENSP00000498222.1	A0A494BZT7
	TOR1A	ENST00000474192.1	TSL:3	n.*90T>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12548 AN: 151892 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0853

Gnomad OTH AF: 0.0891

GnomAD4 exome AF: 0.0722 AC: 9144 AN: 126600 Hom.: 377 Cov.: 0 AF XY: 0.0722 AC XY: 4958 AN XY: 68642

African (AFR) AF: 0.0804 AC: 226 AN: 2812

American (AMR) AF: 0.0698 AC: 296 AN: 4242

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 306 AN: 2814

East Asian (EAS) AF: 0.00320 AC: 15 AN: 4682

South Asian (SAS) AF: 0.0707 AC: 1686 AN: 23850

European-Finnish (FIN) AF: 0.0392 AC: 251 AN: 6406

Middle Eastern (MID) AF: 0.115 AC: 52 AN: 454

European-Non Finnish (NFE) AF: 0.0773 AC: 5813 AN: 75202

Other (OTH) AF: 0.0813 AC: 499 AN: 6138

GnomAD4 genome AF: 0.0826 AC: 12558 AN: 152010 Hom.: 589 Cov.: 32 AF XY: 0.0791 AC XY: 5874 AN XY: 74300

African (AFR) AF: 0.0916 AC: 3790 AN: 41372

American (AMR) AF: 0.0813 AC: 1241 AN: 15264

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

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5170

South Asian (SAS) AF: 0.0781 AC: 376 AN: 4816

European-Finnish (FIN) AF: 0.0398 AC: 422 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0853 AC: 5799 AN: 67998

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.0778 Hom.: 76

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
-	-	1	Early-onset generalized limb-onset dystonia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.80
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1045441; hg19: chr9-132575797;