chr1-179889309-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PVS1_ModerateBP6BA1

The NM_001267578.2(TOR1AIP1):c.554-1G>A variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.624 in 1,582,776 control chromosomes in the GnomAD database, including 311,571 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.60 ( 27524 hom., cov: 32)

Exomes 𝑓: 0.63 ( 284047 hom. )

Consequence

TOR1AIP1
NM_001267578.2 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 4.24

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 made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.034188036 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.8, offset of 3, new splice context is: ttctcttcctatattaacAGtga. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BP6

Variant 1-179889309-G-A is Benign according to our data. Variant chr1-179889309-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257701.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=4}. Variant chr1-179889309-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4 link	c.554-4G>A		splice_region_variant, intron_variant	Intron 2 of 9	ENST00000606911.7	NP_056417.2	Q5JTV8-1
TOR1AIP1	NM_001267578.2 link	c.554-1G>A		splice_acceptor_variant, intron_variant	Intron 2 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.554-4G>A		splice_region_variant, intron_variant	Intron 2 of 9	1	NM_015602.4	ENSP00000476687.1		Q5JTV8-1

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90703

AN:

151850

Hom.:

27499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.663

Gnomad EAS

AF:

0.758

Gnomad SAS

AF:

0.689

Gnomad FIN

AF:

0.558

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.623

Gnomad OTH

AF:

0.624

GnomAD3 exomes

AF:

0.651

AC:

163002

AN:

250292

Hom.:

54000

AF XY:

0.651

AC XY:

88153

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.768

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.760

Gnomad SAS exome

AF:

0.685

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.628

Gnomad OTH exome

AF:

0.649

GnomAD4 exome

AF:

0.627

AC:

896964

AN:

1430808

Hom.:

284047

Cov.:

AF XY:

0.629

AC XY:

448446

AN XY:

712786

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.762

Gnomad4 ASJ exome

AF:

0.658

Gnomad4 EAS exome

AF:

0.753

Gnomad4 SAS exome

AF:

0.686

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.618

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.597

AC:

90767

AN:

151968

Hom.:

27524

Cov.:

AF XY:

0.597

AC XY:

44339

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.682

Gnomad4 ASJ

AF:

0.663

Gnomad4 EAS

AF:

0.757

Gnomad4 SAS

AF:

0.688

Gnomad4 FIN

AF:

0.558

Gnomad4 NFE

AF:

0.623

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.623

Hom.:

42192

Bravo

AF:

0.604

TwinsUK

AF:

0.619

AC:

2294

ALSPAC

AF:

0.608

AC:

2343

ESP6500AA

AF:

0.504

AC:

2219

ESP6500EA

AF:

0.624

AC:

5362

ExAC

AF:

0.646

AC:

78470

Asia WGS

AF:

0.705

AC:

2449

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2Y

Uncertain:1Benign:2

Dec 29, 2019

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 20, 2017

Undiagnosed Diseases Network, NIH

Significance: Uncertain significance

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

- -

not provided

Benign:1

Jul 05, 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

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.96

Eigen

Pathogenic

0.77

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.81

GERP RS

5.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.92

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

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