NM_014506.3:c.134C>T

Variant names:

• chr9-129803346-C-T
• rs2030272378
• NM_014506.3:c.134C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014506.3(TOR1B):​c.134C>T​(p.Ser45Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000696 in 1,436,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: TOR1B NM_014506.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 10 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1B	NM_014506.3	MANE Select	c.134C>T	p.Ser45Phe	missense	Exon 1 of 5	NP_055321.1	O14657
	TOR1B	NM_001317893.2		c.134C>T	p.Ser45Phe	missense	Exon 1 of 4	NP_001304822.1
	TOR1B	NM_001317894.2		c.134C>T	p.Ser45Phe	missense	Exon 1 of 3	NP_001304823.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1B	ENST00000259339.7	TSL:1 MANE Select	c.134C>T	p.Ser45Phe	missense	Exon 1 of 5	ENSP00000259339.2	O14657
	TOR1B	ENST00000931518.1		c.134C>T	p.Ser45Phe	missense	Exon 1 of 5	ENSP00000601577.1
	TOR1B	ENST00000427860.1	TSL:3	c.77C>T	p.Ser26Phe	missense	Exon 1 of 3	ENSP00000411912.1	H0Y7C8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000696 AC: 10 AN: 1436876 Hom.: 0 Cov.: 32 AF XY: 0.00000699 AC XY: 5 AN XY: 715016

African (AFR) AF: 0.00 AC: 0 AN: 30334

American (AMR) AF: 0.00 AC: 0 AN: 42776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25386

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36866

South Asian (SAS) AF: 0.00 AC: 0 AN: 83622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000725 AC: 8 AN: 1103248

Other (OTH) AF: 0.0000168 AC: 1 AN: 59374

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.25
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.34	T
Polyphen		0.99	D
Vest4		0.47
MutPred		0.52		Loss of loop (P = 0.0374)
MVP		0.22
MPC		0.44
ClinPred		0.93	D
GERP RS		5.2
PromoterAI		0.00080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.14
gMVP		0.82
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs2030272378; hg19: chr9-132565625;