chr9-129803397-C-T

Variant names:

• chr9-129803397-C-T
• rs149815190
• NM_014506.3:c.185C>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.185C>T​(p.Pro62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,543,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: TOR1B NM_014506.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0500
• 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=0.1688731).
• BS2: High AC in GnomAdExome4 at 48 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.185C>T	p.Pro62Leu	missense	Exon 1 of 5	NP_055321.1	O14657
	TOR1B	NM_001317893.2		c.185C>T	p.Pro62Leu	missense	Exon 1 of 4	NP_001304822.1
	TOR1B	NM_001317894.2		c.185C>T	p.Pro62Leu	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.185C>T	p.Pro62Leu	missense	Exon 1 of 5	ENSP00000259339.2	O14657
	TOR1B	ENST00000931518.1		c.185C>T	p.Pro62Leu	missense	Exon 1 of 5	ENSP00000601577.1
	TOR1B	ENST00000427860.1	TSL:3	c.128C>T	p.Pro43Leu	missense	Exon 1 of 3	ENSP00000411912.1	H0Y7C8

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 33

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000487 AC: 9 AN: 184992 AF XY: 0.0000762

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000233

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000345 AC: 48 AN: 1391810 Hom.: 0 Cov.: 32 AF XY: 0.0000462 AC XY: 32 AN XY: 692752

African (AFR) AF: 0.00 AC: 0 AN: 28862

American (AMR) AF: 0.00 AC: 0 AN: 37656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24132

East Asian (EAS) AF: 0.00 AC: 0 AN: 32968

South Asian (SAS) AF: 0.000251 AC: 20 AN: 79598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45166

Middle Eastern (MID) AF: 0.000360 AC: 2 AN: 5554

European-Non Finnish (NFE) AF: 0.0000204 AC: 22 AN: 1080764

Other (OTH) AF: 0.0000700 AC: 4 AN: 57110

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74272

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000126 AC: 1

ExAC AF: 0.0000253 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3468

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	0.077
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.050
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.064
Sift	Benign	0.086	T
Sift4G	Benign	0.69	T
Polyphen		0.37	B
Vest4		0.24
MVP		0.082
MPC		0.37
ClinPred		0.037	T
GERP RS		-0.53
PromoterAI		-0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.035
gMVP		0.72
Mutation Taster		=95/5	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: rs149815190; hg19: chr9-132565676;