11-77084942-A-AC
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Strong
The NM_004055.5(CAPN5):c.57dup(p.Cys20LeufsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D19D) has been classified as Likely benign.
Frequency
Consequence
NM_004055.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN5 | NM_004055.5 | c.57dup | p.Cys20LeufsTer17 | frameshift_variant | 2/13 | ENST00000648180.1 | |
CAPN5 | XM_011545225.1 | c.177dup | p.Cys60LeufsTer17 | frameshift_variant | 3/14 | ||
CAPN5 | XM_017018223.3 | c.165dup | p.Cys56LeufsTer17 | frameshift_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN5 | ENST00000648180.1 | c.57dup | p.Cys20LeufsTer17 | frameshift_variant | 2/13 | NM_004055.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250810Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135776
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461606Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727116
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change creates a premature translational stop signal (p.Cys20Leufs*17) in the CAPN5 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CAPN5 cause disease. This variant is present in population databases (rs782363756, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CAPN5-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at