1-179882560-A-AC
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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
NM_015602.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.27
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]
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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 1-179882560-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 |
---|---|---|---|---|---|---|---|---|
TOR1AIP1 | NM_015602.4 | c.63dupC | p.Arg22fs | frameshift_variant | 1/10 | ENST00000606911.7 | NP_056417.2 | |
TOR1AIP1 | NM_001267578.2 | c.63dupC | p.Arg22fs | frameshift_variant | 1/10 | NP_001254507.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TOR1AIP1 | ENST00000606911.7 | c.63dupC | p.Arg22fs | frameshift_variant | 1/10 | 1 | NM_015602.4 | ENSP00000476687.1 | ||
TOR1AIP1 | ENST00000271583.7 | c.63dupC | p.Arg22fs | frameshift_variant | 1/11 | 5 | ENSP00000271583.3 | |||
TOR1AIP1 | ENST00000528443.6 | c.63dupC | p.Arg22fs | frameshift_variant | 1/10 | 2 | ENSP00000435365.2 | |||
ENSG00000272906 | ENST00000610272.1 | n.35dupG | non_coding_transcript_exon_variant | 1/1 | 6 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.38e-7 AC: 1AN: 1355556Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 664226
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1355556
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Cov.:
29
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AC XY:
0
AN XY:
664226
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GnomAD4 genome Cov.: 31
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 submitter | research | Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire | Mar 01, 2024 | PVS1+PM2+PP4 - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.