rs2274955

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The NM_015602.4(TOR1AIP1):c.964+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00233 in 1,612,154 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 118 hom. )

Consequence

TOR1AIP1
NM_015602.4 splice_donor, intron

Scores

Splicing: ADA: 0.9999

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.35

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.032534245 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

BP6

Variant 1-179914055-G-A is Benign according to our data. Variant chr1-179914055-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 476292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-179914055-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4 link	c.964+1G>A		splice_donor_variant, intron_variant	Intron 9 of 9	ENST00000606911.7	NP_056417.2	Q5JTV8-1
TOR1AIP1	NM_001267578.2 link	c.967+1G>A		splice_donor_variant, intron_variant	Intron 9 of 9		NP_001254507.1	Q5JTV8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOR1AIP1	ENST00000606911.7 link	c.964+1G>A		splice_donor_variant, intron_variant	Intron 9 of 9	1	NM_015602.4	ENSP00000476687.1		Q5JTV8-1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

381

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0637

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00560

AC:

1400

AN:

250088

AF XY:

0.00502

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0674

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00232

AC:

3382

AN:

1459868

Hom.:

118

Cov.:

AF XY:

0.00231

AC XY:

1680

AN XY:

726278

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

AC:

AN:

33412

Gnomad4 AMR exome

AF:

0.00310

AC:

138

AN:

44500

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26102

Gnomad4 EAS exome

AF:

0.0709

AC:

2809

AN:

39630

Gnomad4 SAS exome

AF:

0.00178

AC:

153

AN:

85888

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53396

Gnomad4 NFE exome

AF:

0.0000666

AC:

AN:

1110870

Gnomad4 Remaining exome

AF:

0.00343

AC:

207

AN:

60308

Heterozygous variant carriers

143

286

428

571

714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.00251

AC:

382

AN:

152286

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000481

AC:

0.0000481232

AN:

0.0000481232

Gnomad4 AMR

AF:

0.00124

AC:

0.00124151

AN:

0.00124151

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.0638

AC:

0.0638011

AN:

0.0638011

Gnomad4 SAS

AF:

0.00290

AC:

0.00290216

AN:

0.00290216

Gnomad4 FIN

AF:

0.0000944

AC:

0.0000943931

AN:

0.0000943931

Gnomad4 NFE

AF:

0.000162

AC:

0.000161703

AN:

0.000161703

Gnomad4 OTH

AF:

0.00189

AC:

0.00189394

AN:

0.00189394

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

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:

0.00262

Hom.:

Bravo

AF:

0.00323

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00529

AC:

642

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2Y

Benign:3

Apr 11, 2023

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 20, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 25, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.92

GERP RS

5.4

Mutation Taster

=86/14

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

0.93

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.93

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over