9-129814233-G-T

Variant names:

• chr9-129814233-G-T
• rs72755217
• NM_000113.3:c.749-11C>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.749-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,614,012 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (36 hom., cov: 32)
  • Exomes 𝑓: 0.017 (465 hom.)
• Consequence: TOR1A NM_000113.3 intron
• Scores: Splicing: ADA: 0.0001530
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.587
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Illumina, Orphanet
• arthrogryposis multiplex congenita 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-129814233-G-T is Benign according to our data. Variant chr9-129814233-G-T is described in ClinVar as Benign. ClinVar VariationId is 255137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.055 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1A	NM_000113.3	MANE Select	c.749-11C>A		intron	N/A	NP_000104.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1A	ENST00000351698.5	TSL:1 MANE Select	c.749-11C>A		intron	N/A	ENSP00000345719.4
	TOR1A	ENST00000651202.1		c.*17-11C>A		intron	N/A	ENSP00000498222.1
	TOR1A	ENST00000474192.1	TSL:3	n.333-11C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2024 AN: 152078 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00413

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0609

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0173

GnomAD2 exomes AF: 0.0206 AC: 5169 AN: 251308 AF XY: 0.0237

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.0608

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00301

Gnomad NFE exome AF: 0.0162

Gnomad OTH exome AF: 0.0207

GnomAD4 exome AF: 0.0168 AC: 24505 AN: 1461816 Hom.: 465 Cov.: 31 AF XY: 0.0185 AC XY: 13426 AN XY: 727216

African (AFR) AF: 0.00394 AC: 132 AN: 33480

American (AMR) AF: 0.0133 AC: 593 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 1566 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0673 AC: 5803 AN: 86252

European-Finnish (FIN) AF: 0.00326 AC: 174 AN: 53398

Middle Eastern (MID) AF: 0.0583 AC: 335 AN: 5744

European-Non Finnish (NFE) AF: 0.0133 AC: 14738 AN: 1111992

Other (OTH) AF: 0.0192 AC: 1160 AN: 60392

GnomAD4 genome AF: 0.0133 AC: 2025 AN: 152196 Hom.: 36 Cov.: 32 AF XY: 0.0140 AC XY: 1045 AN XY: 74408

African (AFR) AF: 0.00426 AC: 177 AN: 41504

American (AMR) AF: 0.0155 AC: 237 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0608 AC: 293 AN: 4822

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0147 AC: 1000 AN: 68002

Other (OTH) AF: 0.0176 AC: 37 AN: 2108

Alfa AF: 0.0128 Hom.: 7

Bravo AF: 0.0123

Asia WGS AF: 0.0260 AC: 93 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	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	-0.79
CADD	Benign	8.6
DANN	Benign	0.80
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.022
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: rs72755217; hg19: chr9-132576512;