rs2296377

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022371.4(TOR3A):​c.37T>A​(p.Phe13Ile) 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. 14/21 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. F13L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 37)
Exomes 𝑓: 7.4e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TOR3A
NM_022371.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48
Variant links:
Genes affected
TOR3A (HGNC:11997): (torsin family 3 member A) Predicted to enable ATP binding activity. Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.047112256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOR3ANM_022371.4 linkc.37T>A p.Phe13Ile missense_variant Exon 1 of 6 ENST00000367627.8 NP_071766.2 Q9H497-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TOR3AENST00000367627.8 linkc.37T>A p.Phe13Ile missense_variant Exon 1 of 6 1 NM_022371.4 ENSP00000356599.3 Q9H497-1

Frequencies

GnomAD3 genomes
Cov.:
37
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
7.38e-7
AC:
1
AN:
1355330
Hom.:
0
Cov.:
72
AF XY:
0.00
AC XY:
0
AN XY:
669720
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.35e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
37

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
4.8
DANN
Benign
0.85
DEOGEN2
Benign
0.026
T;T;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.27
T;T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.047
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;.;L
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
0.68
N;N;N
REVEL
Benign
0.040
Sift
Benign
0.15
T;T;T
Sift4G
Benign
0.15
T;T;T
Polyphen
0.0030
B;.;.
Vest4
0.16
MutPred
0.28
Gain of MoRF binding (P = 0.0859);Gain of MoRF binding (P = 0.0859);Gain of MoRF binding (P = 0.0859);
MVP
0.16
MPC
0.24
ClinPred
0.063
T
GERP RS
-0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.055
gMVP
0.22

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2296377; hg19: chr1-179051300; API