9-129803397-C-A

Variant names:

• chr9-129803397-C-A
• rs149815190
• NM_014506.3:c.185C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014506.3(TOR1B):​c.185C>A​(p.Pro62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,138 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. 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. P62L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TOR1B NM_014506.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12273988).

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>A	p.Pro62Gln	missense	Exon 1 of 5	NP_055321.1	O14657
	TOR1B	NM_001317893.2		c.185C>A	p.Pro62Gln	missense	Exon 1 of 4	NP_001304822.1
	TOR1B	NM_001317894.2		c.185C>A	p.Pro62Gln	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>A	p.Pro62Gln	missense	Exon 1 of 5	ENSP00000259339.2	O14657
	TOR1B	ENST00000931518.1		c.185C>A	p.Pro62Gln	missense	Exon 1 of 5	ENSP00000601577.1
	TOR1B	ENST00000427860.1	TSL:3	c.128C>A	p.Pro43Gln	missense	Exon 1 of 3	ENSP00000411912.1	H0Y7C8

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152030 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: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1391810 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 79598

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080764

Other (OTH) AF: 0.00 AC: 0 AN: 57110

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74390

African (AFR) AF: 0.00 AC: 0 AN: 41520

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.050
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.039
Sift	Benign	0.17	T
Sift4G	Benign	0.36	T
Polyphen		0.017	B
Vest4		0.22
MutPred		0.41		Gain of helix (P = 0.132)
MVP		0.11
MPC		0.38
ClinPred		0.060	T
GERP RS		-0.53
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.037
gMVP		0.70
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs149815190; hg19: chr9-132565676;