1-179882657-A-G

Variant names:

• chr1-179882657-A-G
• rs139690983
• NM_015602.4:c.155A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015602.4(TOR1AIP1):​c.155A>G​(p.Gln52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q52L) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: TOR1AIP1 NM_015602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 2 publications found

Genes affected

TOR1AIP1 (HGNC:29456): (torsin 1A interacting protein 1) This gene encodes a type 2 integral membrane protein that binds A- and B-type lamins. The encoded protein localizes to the inner nuclear membrane and may be involved in maintaining the attachment of the nuclear membrane to the nuclear lamina during cell division. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2016]

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]

ENSG00000272906 (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=0.034855366).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015602.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1AIP1	NM_015602.4	MANE Select	c.155A>G	p.Gln52Arg	missense	Exon 1 of 10	NP_056417.2
	TOR1AIP1	NM_001267578.2		c.155A>G	p.Gln52Arg	missense	Exon 1 of 10	NP_001254507.1	Q5JTV8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOR1AIP1	ENST00000606911.7	TSL:1 MANE Select	c.155A>G	p.Gln52Arg	missense	Exon 1 of 10	ENSP00000476687.1	Q5JTV8-1
	TOR1AIP1	ENST00000271583.7	TSL:5	c.155A>G	p.Gln52Arg	missense	Exon 1 of 11	ENSP00000271583.3	J3KN66
	TOR1AIP1	ENST00000528443.6	TSL:2	c.155A>G	p.Gln52Arg	missense	Exon 1 of 10	ENSP00000435365.2	Q5JTV8-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151862 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151862 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74172

African (AFR) AF: 0.0000242 AC: 1 AN: 41334

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.74
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.051
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.048
Sift	Benign	0.76	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.061
MutPred		0.092		Gain of MoRF binding (P = 0.0421)
MVP		0.21
MPC		0.11
ClinPred		0.071	T
GERP RS		-0.83
PromoterAI		-0.0033	Neutral
Varity_R		0.070
gMVP		0.031
Mutation Taster		=97/3	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: rs139690983; hg19: chr1-179851792;