20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCT
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong
The NM_000308.4(CTSA):βc.51_56delβ(p.Leu18_Leu19del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000677 in 1,506,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 0)
Exomes π: 0.000074 ( 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 Likely_benign. Variant got -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 20-45891598-CCTGCTG-C is Benign according to our data. Variant chr20-45891598-CCTGCTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 459631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSA | NM_000308.4 | c.51_56del | p.Leu18_Leu19del | inframe_deletion | 2/15 | ENST00000646241.3 | |
CTSA | NM_001127695.3 | c.51_56del | p.Leu18_Leu19del | inframe_deletion | 2/15 | ||
CTSA | NM_001167594.3 | c.51_56del | p.Leu18_Leu19del | inframe_deletion | 2/14 | ||
CTSA | NR_133656.2 | n.96_101del | non_coding_transcript_exon_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSA | ENST00000646241.3 | c.51_56del | p.Leu18_Leu19del | inframe_deletion | 2/15 | NM_000308.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000134 AC: 2AN: 149718Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.000417 AC: 85AN: 203638Hom.: 0 AF XY: 0.000310 AC XY: 35AN XY: 112766
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GnomAD4 exome AF: 0.0000737 AC: 100AN: 1356660Hom.: 0 AF XY: 0.0000696 AC XY: 47AN XY: 674970
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GnomAD4 genome ? AF: 0.0000133 AC: 2AN: 149832Hom.: 0 Cov.: 0 AF XY: 0.0000137 AC XY: 1AN XY: 73032
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Combined deficiency of sialidase AND beta galactosidase Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 08, 2021 | - - |
CTSA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 03, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at