9-129803397-C-G

Variant names:

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

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>G​(p.Pro62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• 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=0.075680375).

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>G	p.Pro62Arg	missense	Exon 1 of 5	NP_055321.1	O14657
	TOR1B	NM_001317893.2		c.185C>G	p.Pro62Arg	missense	Exon 1 of 4	NP_001304822.1
	TOR1B	NM_001317894.2		c.185C>G	p.Pro62Arg	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>G	p.Pro62Arg	missense	Exon 1 of 5	ENSP00000259339.2	O14657
	TOR1B	ENST00000931518.1		c.185C>G	p.Pro62Arg	missense	Exon 1 of 5	ENSP00000601577.1
	TOR1B	ENST00000427860.1	TSL:3	c.128C>G	p.Pro43Arg	missense	Exon 1 of 3	ENSP00000411912.1	H0Y7C8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.58
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N
PhyloP100		0.050
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.034
Sift	Benign	0.29	T
Sift4G	Benign	0.47	T
Polyphen		0.0020	B
Vest4		0.067
MutPred		0.43		Gain of solvent accessibility (P = 0.0808)
MVP		0.093
MPC		0.39
ClinPred		0.21	T
GERP RS		-0.53
PromoterAI		-0.0088	Neutral
Varity_R		0.040
gMVP		0.72
Mutation Taster		=93/7	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;