chr1-179082165-T-C

Variant names:

• chr1-179082165-T-C
• rs2296377
• NM_022371.4:c.37T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022371.4(TOR3A):​c.37T>C​(p.Phe13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,506,738 control chromosomes in the GnomAD database, including 389,643 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.78 (47447 hom., cov: 37)
  • Exomes 𝑓: 0.71 (342196 hom.)
• Consequence: TOR3A NM_022371.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.013119E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR3A	NM_022371.4	c.37T>C	p.Phe13Leu	missense_variant	Exon 1 of 6	ENST00000367627.8	NP_071766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOR3A	ENST00000367627.8	c.37T>C	p.Phe13Leu	missense_variant	Exon 1 of 6	1	NM_022371.4	ENSP00000356599.3

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118815 AN: 152142 Hom.: 47388 Cov.: 37

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.768

GnomAD3 exomes AF: 0.692 AC: 73128 AN: 105614 Hom.: 25802 AF XY: 0.700 AC XY: 42229 AN XY: 60362

Gnomad AFR exome AF: 0.948

Gnomad AMR exome AF: 0.592

Gnomad ASJ exome AF: 0.789

Gnomad EAS exome AF: 0.628

Gnomad SAS exome AF: 0.714

Gnomad FIN exome AF: 0.822

Gnomad NFE exome AF: 0.693

Gnomad OTH exome AF: 0.726

GnomAD4 exome AF: 0.709 AC: 960186 AN: 1354478 Hom.: 342196 Cov.: 72 AF XY: 0.709 AC XY: 474823 AN XY: 669258

Gnomad4 AFR exome AF: 0.954

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.792

Gnomad4 EAS exome AF: 0.665

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.820

Gnomad4 NFE exome AF: 0.699

Gnomad4 OTH exome AF: 0.732

GnomAD4 genome AF: 0.781 AC: 118927 AN: 152260 Hom.: 47447 Cov.: 37 AF XY: 0.784 AC XY: 58342 AN XY: 74460

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.771

Alfa AF: 0.712 Hom.: 40232

Bravo AF: 0.776

TwinsUK AF: 0.707 AC: 2621

ALSPAC AF: 0.701 AC: 2702

ESP6500AA AF: 0.949 AC: 3262

ESP6500EA AF: 0.755 AC: 5365

ExAC AF: 0.663 AC: 67153

Asia WGS AF: 0.724 AC: 2519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.34
DANN	Benign	0.27
DEOGEN2	Benign	0.016	T;T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.21	T;T;T
MetaRNN	Benign	0.0000010	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.60	N;.;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	1.4	N;N;N
REVEL	Benign	0.047
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.052
MutPred		0.16		Gain of MoRF binding (P = 0.1148);Gain of MoRF binding (P = 0.1148);Gain of MoRF binding (P = 0.1148);
MPC		0.20
ClinPred		0.0053	T
GERP RS		-0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.069
gMVP		0.18

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

Other links and lift over

dbSNP: rs2296377; hg19: chr1-179051300; COSMIC: COSV61679607; COSMIC: COSV61679607;