rs749592068

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_015602.4(TOR1AIP1):c.37G>A(p.Glu13Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000257 in 1,480,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E13V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

TOR1AIP1
NM_015602.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 4.14

Publications

0 publications found

Variant links:

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]

TOR1AIP1 links:

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]

TOR1AIP2 links:

ENSG00000272906 (HGNC:):

ENSG00000272906 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026823103).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000591 (9/152184) while in subpopulation EAS AF = 0.00135 (7/5188). AF 95% confidence interval is 0.000633. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOR1AIP1	NM_015602.4	MANE Select	c.37G>A	p.Glu13Lys	missense	Exon 1 of 10	NP_056417.2
TOR1AIP1	NM_001267578.2		c.37G>A	p.Glu13Lys	missense	Exon 1 of 10	NP_001254507.1	Q5JTV8-3
LOC139427322	NM_001436163.1		c.*146G>A		downstream_gene	N/A	NP_001423092.1	A0AAQ5BH39

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TOR1AIP1	ENST00000606911.7	TSL:1 MANE Select	c.37G>A	p.Glu13Lys	missense	Exon 1 of 10	ENSP00000476687.1	Q5JTV8-1
TOR1AIP1	ENST00000271583.7	TSL:5	c.37G>A	p.Glu13Lys	missense	Exon 1 of 11	ENSP00000271583.3	J3KN66
TOR1AIP1	ENST00000528443.6	TSL:2	c.37G>A	p.Glu13Lys	missense	Exon 1 of 10	ENSP00000435365.2	Q5JTV8-3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.0000705

AC:

AN:

113552

AF XY:

0.0000669

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000709

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000549

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000357

GnomAD4 exome

AF:

0.0000218

AC:

AN:

1327830

Hom.:

Cov.:

AF XY:

0.0000123

AC XY:

AN XY:

647868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29158

American (AMR)

AF:

0.00

AC:

AN:

22920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19088

East Asian (EAS)

AF:

0.000194

AC:

AN:

36172

South Asian (SAS)

AF:

0.00

AC:

AN:

65686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5104

European-Non Finnish (NFE)

AF:

0.00000667

AC:

AN:

1049050

Other (OTH)

AF:

0.000275

AC:

AN:

54638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.000957

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000614

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive limb-girdle muscular dystrophy type 2Y (2)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

0.091

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.025

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

4.1

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.5

REVEL

Benign

0.20

Sift

Uncertain

0.016

Sift4G

Pathogenic

0.0

Polyphen

0.94

Vest4

0.28

MVP

0.46

MPC

0.47

ClinPred

0.17

GERP RS

5.3

PromoterAI

0.040

Neutral

(source)

Varity_R

0.12

gMVP

0.22

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over