11-65182882-T-TC
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005186.4(CAPN1):c.181_182insC(p.Phe61fs) 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
CAPN1
NM_005186.4 frameshift
NM_005186.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.42
Genes affected
CAPN1 (HGNC:1476): (calpain 1) The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 1. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 11-65182882-T-TC is Pathogenic according to our data. Variant chr11-65182882-T-TC is described in ClinVar as [Pathogenic]. Clinvar id is 1802257.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CAPN1 | NM_005186.4 | c.181_182insC | p.Phe61fs | frameshift_variant | 2/22 | ENST00000279247.11 | NP_005177.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CAPN1 | ENST00000279247.11 | c.181_182insC | p.Phe61fs | frameshift_variant | 2/22 | 1 | NM_005186.4 | ENSP00000279247.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive spastic paraplegia type 76 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology | Sep 28, 2022 | The c.181_182insC is not present in publicly available population databases like 1000 Genomes, EVS, Indian Exome Database or our in-house exome database. The heterozygous state of the variant is present in ExAC and gnomAD, at a low frequency. The variant has neither been published in literature nor reported to clinical databases like ClinVar, Human Genome Mutation Database (HGMD) and/or OMIM, in any affected individuals. In silico pathogenicity programs like Mutation Taster, CADD, Varsome etc. predicted this variant to be likely deleterious. The variant causes frameshift at the 61st amino acid position of the original transcript, creating a premature stop signal at the 166th amino acid position of the altered transcript, which may either result in translation of a truncated protein or cause nonsense mediated decay of the mRNA. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
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Calibrated prediction
Score
Prediction
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.