20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000308.4(CTSA):c.48_56dup(p.Leu17_Leu19dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
CTSA
NM_000308.4 inframe_insertion
NM_000308.4 inframe_insertion
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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSA | NM_000308.4 | c.48_56dup | p.Leu17_Leu19dup | inframe_insertion | 2/15 | ENST00000646241.3 | |
CTSA | NM_001127695.3 | c.48_56dup | p.Leu17_Leu19dup | inframe_insertion | 2/15 | ||
CTSA | NM_001167594.3 | c.48_56dup | p.Leu17_Leu19dup | inframe_insertion | 2/14 | ||
CTSA | NR_133656.2 | n.93_101dup | non_coding_transcript_exon_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSA | ENST00000646241.3 | c.48_56dup | p.Leu17_Leu19dup | inframe_insertion | 2/15 | NM_000308.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000534 AC: 8AN: 149796Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.0000491 AC: 10AN: 203638Hom.: 0 AF XY: 0.0000798 AC XY: 9AN XY: 112766
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GnomAD4 exome AF: 0.0000251 AC: 36AN: 1432032Hom.: 0 Cov.: 0 AF XY: 0.0000295 AC XY: 21AN XY: 712840
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GnomAD4 genome ? AF: 0.0000534 AC: 8AN: 149796Hom.: 0 Cov.: 0 AF XY: 0.0000548 AC XY: 4AN XY: 72950
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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 | Dec 03, 2021 | This variant, c.102_110dup, results in the insertion of 3 amino acid(s) of the CTSA protein (p.Leu35_Leu37dup), 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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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at