Variant 9-129818942-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000351698.5(TOR1A):c.445-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,609,036 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 9 hom., cov: 31)

Exomes 𝑓: 0.011 ( 121 hom. )

Consequence

TOR1A
ENST00000351698.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0670

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-129818942-C-T is Benign according to our data. Variant chr9-129818942-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-129818942-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0089 (1356/152282) while in subpopulation NFE AF= 0.0136 (925/68022). AF 95% confidence interval is 0.0129. There are 9 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOR1A	NM_000113.3 linkuse as main transcript	c.445-22G>A		intron_variant		ENST00000351698.5	NP_000104.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TOR1A	ENST00000351698.5 linkuse as main transcript	c.445-22G>A	intron_variant	1	NM_000113.3	ENSP00000345719	P1	O14656-1
TOR1A	ENST00000651202.1 linkuse as main transcript	c.541-22G>A	intron_variant			ENSP00000498222
TOR1A	ENST00000473604.2 linkuse as main transcript	n.555-22G>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00892

AC:

1357

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00974

AC:

2389

AN:

245186

Hom.:

AF XY:

0.00965

AC XY:

1285

AN XY:

133148

show subpopulations

Gnomad AFR exome

AF:

0.00249

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00609

Gnomad EAS exome

AF:

0.00999

Gnomad SAS exome

AF:

0.00551

Gnomad FIN exome

AF:

0.0155

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.00955

GnomAD4 exome

AF:

0.0114

AC:

16663

AN:

1456754

Hom.:

121

Cov.:

AF XY:

0.0113

AC XY:

8180

AN XY:

724956

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.00562

Gnomad4 EAS exome

AF:

0.0166

Gnomad4 SAS exome

AF:

0.00563

Gnomad4 FIN exome

AF:

0.0161

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00890

AC:

1356

AN:

152282

Hom.:

Cov.:

AF XY:

0.00841

AC XY:

626

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.0123

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00779

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.3

DANN

Benign

0.88

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over