chr9-129809488-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000259339.7(TOR1B):ā€‹c.916A>Gā€‹(p.Arg306Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

TOR1B
ENST00000259339.7 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0770
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.122749716).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TOR1BNM_014506.3 linkuse as main transcriptc.916A>G p.Arg306Gly missense_variant 5/5 ENST00000259339.7 NP_055321.1 O14657

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TOR1BENST00000259339.7 linkuse as main transcriptc.916A>G p.Arg306Gly missense_variant 5/51 NM_014506.3 ENSP00000259339.2 O14657
TOR1BENST00000427860.1 linkuse as main transcriptc.409-739A>G intron_variant 3 ENSP00000411912.1 H0Y7C8
TOR1BENST00000488169.1 linkuse as main transcriptn.426+456A>G intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152208
Hom.:
0
Cov.:
31
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:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251494
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152208
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsDec 08, 2023The c.916A>G (p.R306G) alteration is located in exon 5 (coding exon 5) of the TOR1B gene. This alteration results from a A to G substitution at nucleotide position 916, causing the arginine (R) at amino acid position 306 to be replaced by a glycine (G). 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
0.098
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
14
DANN
Benign
0.89
DEOGEN2
Benign
0.31
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.14
N
LIST_S2
Uncertain
0.93
D
M_CAP
Uncertain
0.086
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.14
Sift
Benign
0.037
D
Sift4G
Benign
0.14
T
Polyphen
0.077
B
Vest4
0.16
MutPred
0.58
Loss of solvent accessibility (P = 0.0769);
MVP
0.15
MPC
0.49
ClinPred
0.12
T
GERP RS
3.2
Varity_R
0.15
gMVP
0.65

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.

Other links and lift over

dbSNP: rs747153950; hg19: chr9-132571767; API