9-129813548-TAAAA-TAAA

Variant names:

• chr9-129813548-TA-T
• rs573629050
• NM_000113.3:c.*423delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000113.3(TOR1A):​c.*423delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 293,254 control chromosomes in the GnomAD database, including 50 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (18 hom., cov: 32)
  • Exomes 𝑓: 0.016 (32 hom.)
• Consequence: TOR1A NM_000113.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73
• 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: 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 -10 ACMG points.

• BP6: Variant 9-129813548-TA-T is Benign according to our data. Variant chr9-129813548-TA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 365221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0124 (1873/150984) while in subpopulation EAS AF = 0.0202 (104/5144). AF 95% confidence interval is 0.0171. There are 18 homozygotes in GnomAd4. There are 899 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AD,AR gene

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.*423delT		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.*423delT		3_prime_UTR	Exon 5 of 5	ENSP00000345719.4	O14656-1
	TOR1A	ENST00000651202.1		c.*690delT		3_prime_UTR	Exon 6 of 6	ENSP00000498222.1	A0A494BZT7
	TOR1A	ENST00000474192.1	TSL:3	n.*59delT		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1871 AN: 150876 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00460

Gnomad AMI AF: 0.00331

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0186

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.0173

Gnomad FIN AF: 0.00460

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.0163 AC: 2321 AN: 142270 Hom.: 32 Cov.: 0 AF XY: 0.0165 AC XY: 1274 AN XY: 77424

African (AFR) AF: 0.00353 AC: 13 AN: 3686

American (AMR) AF: 0.00927 AC: 43 AN: 4640

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 59 AN: 3326

East Asian (EAS) AF: 0.0197 AC: 106 AN: 5390

South Asian (SAS) AF: 0.0199 AC: 542 AN: 27256

European-Finnish (FIN) AF: 0.00425 AC: 30 AN: 7058

Middle Eastern (MID) AF: 0.0160 AC: 8 AN: 500

European-Non Finnish (NFE) AF: 0.0171 AC: 1428 AN: 83526

Other (OTH) AF: 0.0134 AC: 92 AN: 6888

GnomAD4 genome AF: 0.0124 AC: 1873 AN: 150984 Hom.: 18 Cov.: 32 AF XY: 0.0122 AC XY: 899 AN XY: 73772

African (AFR) AF: 0.00458 AC: 188 AN: 41024

American (AMR) AF: 0.0100 AC: 152 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.0186 AC: 64 AN: 3438

East Asian (EAS) AF: 0.0202 AC: 104 AN: 5144

South Asian (SAS) AF: 0.0176 AC: 84 AN: 4780

European-Finnish (FIN) AF: 0.00460 AC: 48 AN: 10446

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0177 AC: 1200 AN: 67672

Other (OTH) AF: 0.0110 AC: 23 AN: 2096

Alfa AF: 0.00335 Hom.: 1

Bravo AF: 0.0123

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Early-onset generalized limb-onset dystonia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

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: rs573629050; hg19: chr9-132575827;