rs879255612

Positions:

• chr1-179882687-AG-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_015602.4(TOR1AIP1):​c.186delG​(p.Glu62fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TOR1AIP1 NM_015602.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.223

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-179882687-AG-A is Pathogenic according to our data. Variant chr1-179882687-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 253059.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-179882687-AG-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4	c.186delG	p.Glu62fs	frameshift_variant	1/10	ENST00000606911.7	NP_056417.2
TOR1AIP1	NM_001267578.2	c.186delG	p.Glu62fs	frameshift_variant	1/10		NP_001254507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOR1AIP1	ENST00000606911.7	c.186delG	p.Glu62fs	frameshift_variant	1/10	1	NM_015602.4	ENSP00000476687.1
TOR1AIP1	ENST00000271583.7	c.186delG	p.Glu62fs	frameshift_variant	1/11	5		ENSP00000271583.3
TOR1AIP1	ENST00000528443.6	c.186delG	p.Glu62fs	frameshift_variant	1/10	2		ENSP00000435365.2
TOR1AIP1	ENST00000435319.8	c.-178delG		upstream_gene_variant		1		ENSP00000393292.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2Y Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs879255612; hg19: chr1-179851822;