Variant 1-179882506-GCGGGCGA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_015602.4(TOR1AIP1):c.11_17delACGGGCG(p.Asp4GlyfsTer52) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000023 in 1,303,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

TOR1AIP1
NM_015602.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.14

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:

ENSG00000272906 (HGNC:):

ENSG00000272906 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-179882506-GCGGGCGA-G is Pathogenic according to our data. Variant chr1-179882506-GCGGGCGA-G is described in ClinVar as [Pathogenic]. Clinvar id is 959057.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4 link	c.11_17delACGGGCG	p.Asp4GlyfsTer52	frameshift_variant	Exon 1 of 10	ENST00000606911.7	NP_056417.2	Q5JTV8-1
TOR1AIP1	NM_001267578.2 link	c.11_17delACGGGCG	p.Asp4GlyfsTer52	frameshift_variant	Exon 1 of 10		NP_001254507.1	Q5JTV8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TOR1AIP1	ENST00000606911.7 link	c.11_17delACGGGCG	p.Asp4GlyfsTer52	frameshift_variant	Exon 1 of 10	1	NM_015602.4	ENSP00000476687.1	Q5JTV8-1
TOR1AIP1	ENST00000271583.7 link	c.11_17delACGGGCG	p.Asp4GlyfsTer52	frameshift_variant	Exon 1 of 11	5		ENSP00000271583.3	J3KN66
TOR1AIP1	ENST00000528443.6 link	c.11_17delACGGGCG	p.Asp4GlyfsTer52	frameshift_variant	Exon 1 of 10	2		ENSP00000435365.2	Q5JTV8-3
ENSG00000272906	ENST00000610272.1 link	n.83_89delTCGCCCG		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000230

AC:

AN:

1303700

Hom.:

AF XY:

0.00000474

AC XY:

AN XY:

633322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000290

Gnomad4 SAS exome

AF:

0.0000159

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.65e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2Y

Pathogenic:1

Feb 22, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant has not been reported in the literature in individuals with TOR1AIP1-related conditions. This sequence change creates a premature translational stop signal (p.Asp4Glyfs*52) in the TOR1AIP1 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. Loss-of-function variants in TOR1AIP1 are known to be pathogenic (PMID: 4856141, 27342937). For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

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