rs72555383
Positions:
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCT
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCT
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCT
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCT
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CNNNNNNNNNNNNNNNNNNNNNNN
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000308.4(CTSA):βc.45_56delβ(p.Leu16_Leu19del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,581,938 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.000087 ( 0 hom., cov: 0)
Exomes π: 0.000022 ( 0 hom. )
Consequence
CTSA
NM_000308.4 inframe_deletion
NM_000308.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.48
Genes affected
CTSA (HGNC:9251): (cathepsin A) This gene encodes a member of the peptidase S10 family of serine carboxypeptidases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate two chains that comprise the heterodimeric active enzyme. This enzyme possesses deamidase, esterase and carboxypeptidase activities and acts as a scaffold in the lysosomal multienzyme complex. Mutations in this gene are associated with galactosialidosis. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSA | NM_000308.4 | c.45_56del | p.Leu16_Leu19del | inframe_deletion | 2/15 | ENST00000646241.3 | |
CTSA | NM_001127695.3 | c.45_56del | p.Leu16_Leu19del | inframe_deletion | 2/15 | ||
CTSA | NM_001167594.3 | c.45_56del | p.Leu16_Leu19del | inframe_deletion | 2/14 | ||
CTSA | NR_133656.2 | n.90_101del | non_coding_transcript_exon_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSA | ENST00000646241.3 | c.45_56del | p.Leu16_Leu19del | inframe_deletion | 2/15 | NM_000308.4 |
Frequencies
GnomAD3 genomes AF: 0.0000868 AC: 13AN: 149794Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.0000442 AC: 9AN: 203638Hom.: 0 AF XY: 0.0000443 AC XY: 5AN XY: 112766
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GnomAD4 exome AF: 0.0000216 AC: 31AN: 1432030Hom.: 0 AF XY: 0.0000224 AC XY: 16AN XY: 712838
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GnomAD4 genome AF: 0.0000867 AC: 13AN: 149908Hom.: 0 Cov.: 0 AF XY: 0.0000958 AC XY: 7AN XY: 73070
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined deficiency of sialidase AND beta galactosidase Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 11, 2022 | This variant, c.99_110del, results in the deletion of 4 amino acid(s) of the CTSA protein (p.Leu34_Leu37del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CTSA-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at