1-179082165-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 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.

• 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
• Publications: 31 publications found

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]

ENSG00000308086 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022371.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR3A	NM_022371.4	MANE Select	c.37T>C	p.Phe13Leu	missense	Exon 1 of 6	NP_071766.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR3A	ENST00000367627.8	TSL:1 MANE Select	c.37T>C	p.Phe13Leu	missense	Exon 1 of 6	ENSP00000356599.3
	TOR3A	ENST00000352445.10	TSL:1	c.37T>C	p.Phe13Leu	missense	Exon 1 of 6	ENSP00000335351.6
	TOR3A	ENST00000367625.8	TSL:3	c.37T>C	p.Phe13Leu	missense	Exon 1 of 3	ENSP00000356597.4

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

GnomAD2 exomes AF: 0.692 AC: 73128 AN: 105614 AF XY: 0.700

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 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

African (AFR) AF: 0.954 AC: 26279 AN: 27536

American (AMR) AF: 0.605 AC: 19459 AN: 32182

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 18192 AN: 22982

East Asian (EAS) AF: 0.665 AC: 21329 AN: 32064

South Asian (SAS) AF: 0.726 AC: 54988 AN: 75728

European-Finnish (FIN) AF: 0.820 AC: 27918 AN: 34054

Middle Eastern (MID) AF: 0.795 AC: 3293 AN: 4144

European-Non Finnish (NFE) AF: 0.699 AC: 747519 AN: 1069468

Other (OTH) AF: 0.732 AC: 41209 AN: 56320

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

African (AFR) AF: 0.947 AC: 39378 AN: 41586

American (AMR) AF: 0.700 AC: 10713 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2787 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3281 AN: 5164

South Asian (SAS) AF: 0.717 AC: 3464 AN: 4830

European-Finnish (FIN) AF: 0.812 AC: 8627 AN: 10618

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.711 AC: 48319 AN: 67974

Other (OTH) AF: 0.771 AC: 1631 AN: 2116

Alfa AF: 0.715 Hom.: 55812

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 v4.9

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
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.60	N
PhyloP100		-1.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.047
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.052
MutPred		0.16		Gain of MoRF binding (P = 0.1148)
MPC		0.20
ClinPred		0.0053	T
GERP RS		-0.79
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.069
gMVP		0.18
Mutation Taster		=99/1	polymorphism (auto)

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