rs72555383

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000308.4(CTSA):​c.45_56del​(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: 𝑓 0.000087 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

CTSA
NM_000308.4 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48
Variant links:
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]

Genome browser will be placed here

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
CTSANM_000308.4 linkuse as main transcriptc.45_56del p.Leu16_Leu19del inframe_deletion 2/15 ENST00000646241.3
CTSANM_001127695.3 linkuse as main transcriptc.45_56del p.Leu16_Leu19del inframe_deletion 2/15
CTSANM_001167594.3 linkuse as main transcriptc.45_56del p.Leu16_Leu19del inframe_deletion 2/14
CTSANR_133656.2 linkuse as main transcriptn.90_101del non_coding_transcript_exon_variant 2/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTSAENST00000646241.3 linkuse as main transcriptc.45_56del p.Leu16_Leu19del inframe_deletion 2/15 NM_000308.4 P10619-1

Frequencies

GnomAD3 genomes
AF:
0.0000868
AC:
13
AN:
149794
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000270
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000667
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000485
GnomAD3 exomes
AF:
0.0000442
AC:
9
AN:
203638
Hom.:
0
AF XY:
0.0000443
AC XY:
5
AN XY:
112766
show subpopulations
Gnomad AFR exome
AF:
0.000751
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000216
AC:
31
AN:
1432030
Hom.:
0
AF XY:
0.0000224
AC XY:
16
AN XY:
712838
show subpopulations
Gnomad4 AFR exome
AF:
0.000517
Gnomad4 AMR exome
AF:
0.0000229
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000823
Gnomad4 OTH exome
AF:
0.0000338
GnomAD4 genome
AF:
0.0000867
AC:
13
AN:
149908
Hom.:
0
Cov.:
0
AF XY:
0.0000958
AC XY:
7
AN XY:
73070
show subpopulations
Gnomad4 AFR
AF:
0.000269
Gnomad4 AMR
AF:
0.0000666
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000480

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 submitterclinical testingInvitaeAug 11, 2022This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs72555383; hg19: chr20-44520237; API