dbSNP rs2030272378: TOR1B:p.Ser45Tyr (chr9-129803346-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014506.3(TOR1B):c.134C>A(p.Ser45Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S45F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TOR1B
NM_014506.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.70

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014506.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOR1B	NM_014506.3	MANE Select	c.134C>A	p.Ser45Tyr	missense	Exon 1 of 5	NP_055321.1	O14657
TOR1B	NM_001317893.2		c.134C>A	p.Ser45Tyr	missense	Exon 1 of 4	NP_001304822.1
TOR1B	NM_001317894.2		c.134C>A	p.Ser45Tyr	missense	Exon 1 of 3	NP_001304823.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOR1B	ENST00000259339.7	TSL:1 MANE Select	c.134C>A	p.Ser45Tyr	missense	Exon 1 of 5	ENSP00000259339.2	O14657
TOR1B	ENST00000931518.1		c.134C>A	p.Ser45Tyr	missense	Exon 1 of 5	ENSP00000601577.1
TOR1B	ENST00000427860.1	TSL:3	c.77C>A	p.Ser26Tyr	missense	Exon 1 of 3	ENSP00000411912.1	H0Y7C8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1436874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715014

African (AFR)

AF:

0.00

AC:

AN:

30334

American (AMR)

AF:

0.00

AC:

AN:

42776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25386

East Asian (EAS)

AF:

0.00

AC:

AN:

36866

South Asian (SAS)

AF:

0.00

AC:

AN:

83622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103246

Other (OTH)

AF:

0.00

AC:

AN:

59374

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.78

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.4

PhyloP100

4.7

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.2

REVEL

Benign

0.21

Sift

Benign

0.078

Sift4G

Benign

0.50

Polyphen

0.99

Vest4

0.54

MutPred

0.51

Loss of loop (P = 0.0374)

MVP

0.24

MPC

0.89

ClinPred

0.95

GERP RS

5.2

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.095

gMVP

0.84

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over