20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCTGCT
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000308.4(CTSA):βc.54_56delβ(p.Leu19del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,575,580 control chromosomes in the GnomAD database, including 278,356 homozygotes. Variant has been reported in ClinVar as Benign (β β ).
Frequency
Genomes: π 0.66 ( 31868 hom., cov: 0)
Exomes π: 0.61 ( 246488 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 Benign. Variant got -16 ACMG points.
BP6
?
Variant 20-45891598-CCTG-C is Benign according to our data. Variant chr20-45891598-CCTG-C is described in ClinVar as [Benign]. Clinvar id is 195059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-45891598-CCTG-C is described in Lovd as [Benign]. Variant chr20-45891598-CCTG-C is described in Lovd as [Likely_benign]. Variant chr20-45891598-CCTG-C is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTSA | NM_000308.4 | c.54_56del | p.Leu19del | inframe_deletion | 2/15 | ENST00000646241.3 | |
CTSA | NM_001127695.3 | c.54_56del | p.Leu19del | inframe_deletion | 2/15 | ||
CTSA | NM_001167594.3 | c.54_56del | p.Leu19del | inframe_deletion | 2/14 | ||
CTSA | NR_133656.2 | n.99_101del | non_coding_transcript_exon_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTSA | ENST00000646241.3 | c.54_56del | p.Leu19del | inframe_deletion | 2/15 | NM_000308.4 |
Frequencies
GnomAD3 genomes ? AF: 0.655 AC: 98069AN: 149708Hom.: 31815 Cov.: 0
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GnomAD3 exomes AF: 0.623 AC: 126967AN: 203638Hom.: 37576 AF XY: 0.620 AC XY: 69969AN XY: 112766
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GnomAD4 exome AF: 0.607 AC: 865716AN: 1425758Hom.: 246488 AF XY: 0.606 AC XY: 430222AN XY: 709556
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GnomAD4 genome ? AF: 0.655 AC: 98180AN: 149822Hom.: 31868 Cov.: 0 AF XY: 0.657 AC XY: 47994AN XY: 73024
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ClinVar
Significance: Benign
Submissions summary: Benign:13
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 19, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 64% of total chromosomes in ExAC - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 06, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:4
Benign, flagged submission | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 22, 2017 | Variant summary: The CTSA c.108_110delGCT (p.Leu37del) variant involves the deletion of a luecine in a string of 9 leucines. One in silico tool predicts a polymorphism outcome for this variant. This variant was found in 144801/230752 control chromosomes (43432 homozygotes) at a frequency of 0.6275179, which is approximately 397 times the estimated maximal expected allele frequency of a pathogenic CTSA variant (0.0015811), suggesting this variant is likely a benign polymorphism. Taken together, this variant is classified as benign. One case report cites the variant in a GSL patient, along with two other variants that have not been reported by other clinical labs, therefore it is unclear which variants are disease-causing. Multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 13, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 15, 2017 | - - |
Combined deficiency of sialidase AND beta galactosidase Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | May 04, 2023 | Latino/Admixed American population allele frequency is 68.93%% (rs781707830, 126967/203638 alleles, 37576 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.1.0, this variant is classified as BENIGN. Following criteria are met: BA1 - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at