rs1281378

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015602.4(TOR1AIP1):c.437T>C(p.Met146Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,613,344 control chromosomes in the GnomAD database, including 323,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26558 hom., cov: 32)

Exomes 𝑓: 0.63 ( 296470 hom. )

Consequence

TOR1AIP1
NM_015602.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.476

Publications

40 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 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy type 2Y
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

TOR1AIP1 links:

ENSG00000272906 (HGNC:):

ENSG00000272906 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4708805E-6).

BP6

Variant 1-179882939-T-C is Benign according to our data. Variant chr1-179882939-T-C is described in ClinVar as Benign. ClinVar VariationId is 257699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4 link	c.437T>C	p.Met146Thr	missense_variant	Exon 1 of 10	ENST00000606911.7	NP_056417.2	Q5JTV8-1
TOR1AIP1	NM_001267578.2 link	c.437T>C	p.Met146Thr	missense_variant	Exon 1 of 10		NP_001254507.1	Q5JTV8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOR1AIP1	ENST00000606911.7 link	c.437T>C	p.Met146Thr	missense_variant	Exon 1 of 10	1	NM_015602.4	ENSP00000476687.1		Q5JTV8-1

Frequencies

GnomAD3 genomes

AF:

0.581

AC:

88369

AN:

152014

Hom.:

26537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.627

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.657

Gnomad EAS

AF:

0.758

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.609

GnomAD2 exomes

AF:

0.650

AC:

160644

AN:

247320

AF XY:

0.649

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.765

Gnomad ASJ exome

AF:

0.659

Gnomad EAS exome

AF:

0.760

Gnomad FIN exome

AF:

0.571

Gnomad NFE exome

AF:

0.636

Gnomad OTH exome

AF:

0.645

GnomAD4 exome

AF:

0.635

AC:

927200

AN:

1461212

Hom.:

296470

Cov.:

AF XY:

0.636

AC XY:

462164

AN XY:

726872

show subpopulations

African (AFR)

AF:

0.424

AC:

14185

AN:

33476

American (AMR)

AF:

0.759

AC:

33925

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.654

AC:

17091

AN:

26130

East Asian (EAS)

AF:

0.753

AC:

29889

AN:

39686

South Asian (SAS)

AF:

0.671

AC:

57879

AN:

86240

European-Finnish (FIN)

AF:

0.568

AC:

30183

AN:

53134

Middle Eastern (MID)

AF:

0.654

AC:

3773

AN:

5766

European-Non Finnish (NFE)

AF:

0.631

AC:

702041

AN:

1111740

Other (OTH)

AF:

0.633

AC:

38234

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

19280

38559

57839

77118

96398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18676

37352

56028

74704

93380

<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:

0.581

AC:

88423

AN:

152132

Hom.:

26558

Cov.:

AF XY:

0.581

AC XY:

43214

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.424

AC:

17598

AN:

41506

American (AMR)

AF:

0.677

AC:

10358

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.657

AC:

2280

AN:

3470

East Asian (EAS)

AF:

0.757

AC:

3899

AN:

5148

South Asian (SAS)

AF:

0.673

AC:

3241

AN:

4814

European-Finnish (FIN)

AF:

0.567

AC:

6002

AN:

10586

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.632

AC:

42982

AN:

67990

Other (OTH)

AF:

0.613

AC:

1294

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1864

3728

5591

7455

9319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.622

Hom.:

93923

Bravo

AF:

0.584

TwinsUK

AF:

0.629

AC:

2333

ALSPAC

AF:

0.620

AC:

2389

ESP6500AA

AF:

0.444

AC:

1953

ESP6500EA

AF:

0.633

AC:

5433

ExAC

AF:

0.640

AC:

77614

Asia WGS

AF:

0.697

AC:

2422

AN:

3478

EpiCase

AF:

0.641

EpiControl

AF:

0.640

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2Y

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.94

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.016

.;.;T;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.52

T;T;T;T;T

MetaRNN

Benign

0.0000015

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

N;.;N;.;.

PhyloP100

0.48

PrimateAI

Benign

0.42

PROVEAN

Benign

1.4

N;N;.;.;N

REVEL

Benign

0.033

Sift

Benign

1.0

T;T;.;.;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;.;B;.;.

Vest4

0.037

MPC

0.12

ClinPred

0.0043

GERP RS

-1.5

PromoterAI

0.070

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.12

gMVP

0.030

Mutation Taster

=99/1

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over