20-45892794-CTT-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000308.4(CTSA):c.517_518delTT(p.Phe173ProfsTer39) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CTSA
NM_000308.4 frameshift
NM_000308.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.98
Publications
0 publications found
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]
CTSA Gene-Disease associations (from GenCC):
- galactosialidosisInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Illumina, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 20-45892794-CTT-C is Pathogenic according to our data. Variant chr20-45892794-CTT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000308.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CTSA | MANE Select | c.517_518delTT | p.Phe173ProfsTer39 | frameshift | Exon 6 of 15 | NP_000299.3 | P10619-1 | ||
| CTSA | c.517_518delTT | p.Phe173ProfsTer39 | frameshift | Exon 6 of 15 | NP_001121167.1 | P10619-1 | |||
| CTSA | c.466_467delTT | p.Phe156ProfsTer39 | frameshift | Exon 5 of 14 | NP_001161066.2 | P10619-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CTSA | MANE Select | c.517_518delTT | p.Phe173ProfsTer39 | frameshift | Exon 6 of 15 | ENSP00000493613.2 | P10619-1 | ||
| CTSA | TSL:1 | c.571_572delTT | p.Phe191ProfsTer39 | frameshift | Exon 6 of 15 | ENSP00000361562.3 | X6R8A1 | ||
| CTSA | TSL:1 | c.517_518delTT | p.Phe173ProfsTer39 | frameshift | Exon 6 of 15 | ENSP00000191018.5 | P10619-1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152214
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461882Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727246 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461882
Hom.:
AF XY:
AC XY:
3
AN XY:
727246
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1112006
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
1
2
2
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4
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152214
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74364
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41454
American (AMR)
AF:
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68038
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
3
-
-
Combined deficiency of sialidase AND beta galactosidase (3)
1
-
-
GALACTOSIALIDOSIS, LATE INFANTILE (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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