1-179882560-A-AC

Variant summary

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

The NM_015602.4(TOR1AIP1):​c.63dupC​(p.Arg22fs) 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 (★). Synonymous variant affecting the same amino acid position (i.e. R22R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 7.4e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TOR1AIP1
NM_015602.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.27
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]

Genome browser will be placed here

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 1-179882560-A-AC is Pathogenic according to our data. Variant chr1-179882560-A-AC is described in ClinVar as [Pathogenic]. Clinvar id is 3233244.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TOR1AIP1NM_015602.4 linkuse as main transcriptc.63dupC p.Arg22fs frameshift_variant 1/10 ENST00000606911.7 NP_056417.2 Q5JTV8-1
TOR1AIP1NM_001267578.2 linkuse as main transcriptc.63dupC p.Arg22fs frameshift_variant 1/10 NP_001254507.1 Q5JTV8-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TOR1AIP1ENST00000606911.7 linkuse as main transcriptc.63dupC p.Arg22fs frameshift_variant 1/101 NM_015602.4 ENSP00000476687.1 Q5JTV8-1
TOR1AIP1ENST00000271583.7 linkuse as main transcriptc.63dupC p.Arg22fs frameshift_variant 1/115 ENSP00000271583.3 J3KN66
TOR1AIP1ENST00000528443.6 linkuse as main transcriptc.63dupC p.Arg22fs frameshift_variant 1/102 ENSP00000435365.2 Q5JTV8-3
ENSG00000272906ENST00000610272.1 linkuse as main transcriptn.35dupG non_coding_transcript_exon_variant 1/16

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
7.38e-7
AC:
1
AN:
1355556
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
664226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000145
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Centronuclear myopathy Pathogenic:1
Pathogenic, criteria provided, single submitterresearchMuscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et CellulaireMar 01, 2024PVS1+PM2+PP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-179851695; API