9-129803219-C-T

Variant names:

• chr9-129803219-C-T
• rs1331052366
• NM_014506.3:c.7C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014506.3(TOR1B):​c.7C>T​(p.Arg3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,348,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: TOR1B NM_014506.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.180
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19193831).
• BS2: High AC in GnomAdExome4 at 26 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.7C>T	p.Arg3Trp	missense	Exon 1 of 5	NP_055321.1	O14657
	TOR1B	NM_001317893.2		c.7C>T	p.Arg3Trp	missense	Exon 1 of 4	NP_001304822.1
	TOR1B	NM_001317894.2		c.7C>T	p.Arg3Trp	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.7C>T	p.Arg3Trp	missense	Exon 1 of 5	ENSP00000259339.2	O14657
	TOR1B	ENST00000931518.1		c.7C>T	p.Arg3Trp	missense	Exon 1 of 5	ENSP00000601577.1
	TOR1B	ENST00000486372.1	TSL:2	n.63C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000193 AC: 26 AN: 1348874 Hom.: 0 Cov.: 31 AF XY: 0.0000239 AC XY: 16 AN XY: 668240

African (AFR) AF: 0.00 AC: 0 AN: 27594

American (AMR) AF: 0.00 AC: 0 AN: 30602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20672

East Asian (EAS) AF: 0.00 AC: 0 AN: 33802

South Asian (SAS) AF: 0.00 AC: 0 AN: 72520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4234

European-Non Finnish (NFE) AF: 0.0000244 AC: 26 AN: 1065684

Other (OTH) AF: 0.00 AC: 0 AN: 55406

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.51
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.18
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.082
Sift	Benign	0.18	T
Sift4G	Uncertain	0.035	D
Polyphen		0.95	P
Vest4		0.13
MutPred		0.41		Loss of disorder (P = 0.001)
MVP		0.068
MPC		0.38
ClinPred		0.47	T
GERP RS		2.2
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.041
gMVP		0.81
Mutation Taster		=93/7	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: rs1331052366; hg19: chr9-132565498;