1-179908645-A-C

Variant names:

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.879A>C(p.Gln293His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 1,612,082 control chromosomes in the GnomAD database, including 3,475 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 0.053 ( 320 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3155 hom. )

Consequence

TOR1AIP1
NM_015602.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0120

Publications

21 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:

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=0.002154529).

BP6

Variant 1-179908645-A-C is Benign according to our data. Variant chr1-179908645-A-C is described in ClinVar as Benign. ClinVar VariationId is 257704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4 link	c.879A>C	p.Gln293His	missense_variant	Exon 8 of 10	ENST00000606911.7	NP_056417.2	Q5JTV8-1
TOR1AIP1	NM_001267578.2 link	c.882A>C	p.Gln294His	missense_variant	Exon 8 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.879A>C	p.Gln293His	missense_variant	Exon 8 of 10	1	NM_015602.4	ENSP00000476687.1		Q5JTV8-1

Frequencies

GnomAD3 genomes

AF:

0.0535

AC:

8143

AN:

152174

Hom.:

319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0207

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0566

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00288

Gnomad SAS

AF:

0.0402

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0676

Gnomad OTH

AF:

0.0530

GnomAD2 exomes

AF:

0.0555

AC:

13934

AN:

251038

AF XY:

0.0567

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.0439

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.0647

Gnomad OTH exome

AF:

0.0560

GnomAD4 exome

AF:

0.0608

AC:

88741

AN:

1459790

Hom.:

3155

Cov.:

AF XY:

0.0607

AC XY:

44052

AN XY:

726314

show subpopulations

African (AFR)

AF:

0.0195

AC:

651

AN:

33458

American (AMR)

AF:

0.0428

AC:

1910

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

292

AN:

26102

East Asian (EAS)

AF:

0.00197

AC:

AN:

39650

South Asian (SAS)

AF:

0.0460

AC:

3969

AN:

86192

European-Finnish (FIN)

AF:

0.134

AC:

7133

AN:

53304

Middle Eastern (MID)

AF:

0.0255

AC:

147

AN:

5764

European-Non Finnish (NFE)

AF:

0.0642

AC:

71266

AN:

1110358

Other (OTH)

AF:

0.0546

AC:

3295

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

3833

7667

11500

15334

19167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2540

5080

7620

10160

12700

<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:

0.0535

AC:

8142

AN:

152292

Hom.:

320

Cov.:

AF XY:

0.0555

AC XY:

4134

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0207

AC:

859

AN:

41564

American (AMR)

AF:

0.0565

AC:

865

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3472

East Asian (EAS)

AF:

0.00327

AC:

AN:

5192

South Asian (SAS)

AF:

0.0398

AC:

192

AN:

4824

European-Finnish (FIN)

AF:

0.135

AC:

1436

AN:

10606

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0676

AC:

4600

AN:

68016

Other (OTH)

AF:

0.0520

AC:

110

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

392

785

1177

1570

1962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0552

Hom.:

841

Bravo

AF:

0.0446

TwinsUK

AF:

0.0650

AC:

241

ALSPAC

AF:

0.0638

AC:

246

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.0623

AC:

536

ExAC

AF:

0.0560

AC:

6796

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0575

EpiControl

AF:

0.0549

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

- -

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

0.13

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.6

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.065

.;.;T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.63

T;T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;.;L;.;.

PhyloP100

-0.012

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

N;N;.;.;.

REVEL

Benign

0.010

Sift

Benign

0.14

T;T;.;.;.

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.0020

.;.;B;.;.

Vest4

0.11

MutPred

0.23

.;.;Loss of MoRF binding (P = 0.0954);.;.;

MPC

0.097

ClinPred

0.0056

GERP RS

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.39

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