rs3737813

Variant names:

• chr1-179860877-A-C
• rs3737813
• NM_001199260.2:c.-147+4559T>G

Variant summary

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

The NM_022347.5(TOR1AIP2):​c.*3904T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 985,348 control chromosomes in the GnomAD database, including 14,678 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1796 hom., cov: 32)
  • Exomes 𝑓: 0.17 (12882 hom.)
• Consequence: TOR1AIP2 NM_022347.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

TOR1AIP2 (HGNC:24055): (torsin 1A interacting protein 2) One of the two protein isoforms encoded by this gene is a type II integral membrane protein found in the endoplasmic reticulum (ER). The encoded protein is a cofactor for the ATPase TorsinA, regulating the amount of TorsinA present in the ER compared to that found in the nuclear envelope. Defects in this protein are a cause of early onset primary dystonia, a neuromuscular disease. The other isoform encoded by this gene is an interferon alpha responsive protein whose cellular role has yet to be determined. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP2	NM_001199260.2	c.-147+4559T>G		intron_variant	Intron 3 of 6	ENST00000609928.6	NP_001186189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOR1AIP2	ENST00000609928.6	c.-147+4559T>G		intron_variant	Intron 3 of 6	2	NM_001199260.2	ENSP00000477486.1
TOR1AIP2	ENST00000367612.7	c.-146-8066T>G		intron_variant	Intron 2 of 5	1		ENSP00000356584.3
TOR1AIP2	ENST00000482587	c.*3904T>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000485355.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21256 AN: 152122 Hom.: 1794 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.174 AC: 144866 AN: 833108 Hom.: 12882 Cov.: 32 AF XY: 0.175 AC XY: 67196 AN XY: 384714

Gnomad4 AFR exome AF: 0.0414

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.0891

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.140 AC: 21252 AN: 152240 Hom.: 1796 Cov.: 32 AF XY: 0.144 AC XY: 10704 AN XY: 74440

Gnomad4 AFR AF: 0.0534

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.125

Alfa AF: 0.155 Hom.: 2686

Bravo AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.75

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: rs3737813; hg19: chr1-179830012;