Variant 9-129804323-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000259339.7(TOR1B):c.450G>T(p.Lys150Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

TOR1B
ENST00000259339.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.63

Variant links:

Genes affected

TOR1B (HGNC:11995): (torsin family 1 member B) The protein encoded by this gene is an ATPase found primarily in the endoplasmic reticulum and nuclear envelope. This gene has a highly-similar neighboring gene, TOR1A, that encodes a protein that is likely to interact in a complex with this protein. Finally, this protein may act as a chaperone and play a role in maintaining the integrity of the nuclear envelope and endoplasmic reticulum. Several transcript variants, some protein-coding and others non-protein coding, have been found for this gene. [provided by RefSeq, Dec 2015]

TOR1B links:

TOR1B (HGNC:):

TOR1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03216663).

BS2

High AC in GnomAdExome4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOR1B	NM_014506.3 linkuse as main transcript	c.450G>T	p.Lys150Asn	missense_variant	2/5	ENST00000259339.7	NP_055321.1	O14657

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TOR1B	ENST00000259339.7 linkuse as main transcript	c.450G>T	p.Lys150Asn	missense_variant	2/5	1	NM_014506.3	ENSP00000259339.2	O14657
TOR1B	ENST00000427860.1 linkuse as main transcript	c.393G>T	p.Lys131Asn	missense_variant	2/3	3		ENSP00000411912.1	H0Y7C8
TOR1B	ENST00000486372.1 linkuse as main transcript	n.506G>T		non_coding_transcript_exon_variant	2/2	2
TOR1B	ENST00000488169.1 linkuse as main transcript	n.-35G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

250350

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1460414

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

726138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.450G>T (p.K150N) alteration is located in exon 2 (coding exon 2) of the TOR1B gene. This alteration results from a G to T substitution at nucleotide position 450, causing the lysine (K) at amino acid position 150 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.062

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.23

M_CAP

Benign

0.0027

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.77

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

0.40

REVEL

Benign

0.068

Sift

Benign

0.78

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.13

MutPred

0.41

Loss of methylation at K150 (P = 0.0122);

MVP

0.082

MPC

0.43

ClinPred

0.019

GERP RS

-1.2

Varity_R

0.068

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.20

Position offset: 15

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