9-129813556-A-AC

Variant summary

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

The NM_000113.3(TOR1A):c.*415_*416insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 300,522 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (1 hom.)
• Consequence: TOR1A NM_000113.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30

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 9-129813556-A-AC is Benign according to our data. Variant chr9-129813556-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 365222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00775 (1176/151738) while in subpopulation AFR AF= 0.0265 (1096/41312). AF 95% confidence interval is 0.0252. There are 13 homozygotes in gnomad4. There are 572 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOR1A	NM_000113.3	c.*415_*416insG		3_prime_UTR_variant	5/5	ENST00000351698.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOR1A	ENST00000351698.5	c.*415_*416insG		3_prime_UTR_variant	5/5	1	NM_000113.3	P1
TOR1A	ENST00000651202.1	c.*682_*683insG		3_prime_UTR_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.00775 AC: 1175 AN: 151620 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00335

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00672

GnomAD4 exome AF: 0.000591 AC: 88 AN: 148784 Hom.: 1 Cov.: 0 AF XY: 0.000508 AC XY: 41 AN XY: 80778

Gnomad4 AFR exome AF: 0.0174

Gnomad4 AMR exome AF: 0.00124

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000714

Gnomad4 SAS exome AF: 0.0000700

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000458

Gnomad4 OTH exome AF: 0.000830

GnomAD4 genome AF: 0.00775 AC: 1176 AN: 151738 Hom.: 13 Cov.: 32 AF XY: 0.00770 AC XY: 572 AN XY: 74250

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.00334

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00665

Alfa AF: 0.00632 Hom.: 0

Bravo AF: 0.00880

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: rs60745320; hg19: chr9-132575835;