1-179082165-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 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.

• Frequency:
  • Genomes: not found (cov: 37)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -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
TOR3A	NM_022371.4	c.37T>A	p.Phe13Ile	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>A	p.Phe13Ile	missense_variant	Exon 1 of 6	1	NM_022371.4	ENSP00000356599.3

Frequencies

GnomAD3 genomes Cov.: 37

GnomAD2 exomes AF: 0.00 AC: 0 AN: 105614 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 27540

American (AMR) AF: 0.00 AC: 0 AN: 32320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23028

East Asian (EAS) AF: 0.00 AC: 0 AN: 32112

South Asian (SAS) AF: 0.00 AC: 0 AN: 75878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4146

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069872

Other (OTH) AF: 0.00 AC: 0 AN: 56360

GnomAD4 genome Cov.: 37

Alfa AF: 0.00 Hom.: 55812

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
PhyloP100		-1.5
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
Vest4		0.16
ClinPred		0.063	T
GERP RS		-0.79
PromoterAI		-0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.055
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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;