9-129813548-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000113.3(TOR1A):c.*423del 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOR1A	NM_000113.3	c.*423del		3_prime_UTR_variant	5/5	ENST00000351698.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOR1A	ENST00000351698.5	c.*423del		3_prime_UTR_variant	5/5	1	NM_000113.3	P1
TOR1A	ENST00000651202.1	c.*690del		3_prime_UTR_variant	6/6

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

Gnomad4 AFR exome AF: 0.00353

Gnomad4 AMR exome AF: 0.00927

Gnomad4 ASJ exome AF: 0.0177

Gnomad4 EAS exome AF: 0.0197

Gnomad4 SAS exome AF: 0.0199

Gnomad4 FIN exome AF: 0.00425

Gnomad4 NFE exome AF: 0.0171

Gnomad4 OTH exome AF: 0.0134

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

Gnomad4 AFR AF: 0.00458

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.0186

Gnomad4 EAS AF: 0.0202

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.00460

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0110

Bravo AF: 0.0123

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early-onset generalized limb-onset dystonia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs573629050; hg19: chr9-132575827;