1-179917990-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015602.4(TOR1AIP1):c.1503G>A(p.Ala501Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 1,614,166 control chromosomes in the GnomAD database, including 728,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66292 hom., cov: 33)

Exomes 𝑓: 0.95 ( 662548 hom. )

Consequence

TOR1AIP1
NM_015602.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0140

Publications

24 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.152).

BP6

Variant 1-179917990-G-A is Benign according to our data. Variant chr1-179917990-G-A is described in ClinVar as Benign. ClinVar VariationId is 257698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.014 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4 link	c.1503G>A	p.Ala501Ala	synonymous_variant	Exon 10 of 10	ENST00000606911.7	NP_056417.2	Q5JTV8-1
TOR1AIP1	NM_001267578.2 link	c.1506G>A	p.Ala502Ala	synonymous_variant	Exon 10 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.1503G>A	p.Ala501Ala	synonymous_variant	Exon 10 of 10	1	NM_015602.4	ENSP00000476687.1		Q5JTV8-1

Frequencies

GnomAD3 genomes

AF:

0.932

AC:

141871

AN:

152154

Hom.:

66244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.987

Gnomad AMR

AF:

0.948

Gnomad ASJ

AF:

0.954

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.981

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.955

Gnomad OTH

AF:

0.928

GnomAD2 exomes

AF:

0.950

AC:

238682

AN:

251342

AF XY:

0.951

show subpopulations

Gnomad AFR exome

AF:

0.875

Gnomad AMR exome

AF:

0.962

Gnomad ASJ exome

AF:

0.957

Gnomad EAS exome

AF:

0.900

Gnomad FIN exome

AF:

0.979

Gnomad NFE exome

AF:

0.956

Gnomad OTH exome

AF:

0.956

GnomAD4 exome

AF:

0.952

AC:

1391452

AN:

1461894

Hom.:

662548

Cov.:

AF XY:

0.952

AC XY:

692399

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.869

AC:

29107

AN:

33480

American (AMR)

AF:

0.961

AC:

42978

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.957

AC:

25013

AN:

26136

East Asian (EAS)

AF:

0.900

AC:

35720

AN:

39700

South Asian (SAS)

AF:

0.956

AC:

82468

AN:

86258

European-Finnish (FIN)

AF:

0.979

AC:

52299

AN:

53420

Middle Eastern (MID)

AF:

0.930

AC:

5364

AN:

5768

European-Non Finnish (NFE)

AF:

0.954

AC:

1061260

AN:

1112012

Other (OTH)

AF:

0.948

AC:

57243

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

4591

9181

13772

18362

22953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21616

43232

64848

86464

108080

<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:

0.932

AC:

141977

AN:

152272

Hom.:

66292

Cov.:

AF XY:

0.933

AC XY:

69488

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.876

AC:

36383

AN:

41534

American (AMR)

AF:

0.948

AC:

14490

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.954

AC:

3312

AN:

3472

East Asian (EAS)

AF:

0.905

AC:

4685

AN:

5176

South Asian (SAS)

AF:

0.952

AC:

4598

AN:

4830

European-Finnish (FIN)

AF:

0.981

AC:

10411

AN:

10616

Middle Eastern (MID)

AF:

0.969

AC:

285

AN:

294

European-Non Finnish (NFE)

AF:

0.955

AC:

64951

AN:

68036

Other (OTH)

AF:

0.929

AC:

1964

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

516

1032

1547

2063

2579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.948

Hom.:

59754

Bravo

AF:

0.926

Asia WGS

AF:

0.931

AC:

3238

AN:

3478

EpiCase

AF:

0.952

EpiControl

AF:

0.955

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

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.7

(source)

DANN

Benign

0.63

PhyloP100

-0.014

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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