Genetic Variant CTSA:p.Leu18_Leu19del (chr20-45891598-CCTGCTG-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The NM_000308.4(CTSA):c.51_56delGCTGCT(p.Leu18_Leu19del) variant causes a disruptive 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 (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

CTSA
NM_000308.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

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]

CTSA links:

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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 rank	MANE	Protein	UniProt
CTSA	NM_000308.4 link	c.51_56delGCTGCT	p.Leu18_Leu19del	disruptive_inframe_deletion	Exon 2 of 15	ENST00000646241.3	NP_000299.3	P10619-1X6R8A1
CTSA	NM_001127695.3 link	c.51_56delGCTGCT	p.Leu18_Leu19del	disruptive_inframe_deletion	Exon 2 of 15		NP_001121167.1	P10619-1
CTSA	NM_001167594.3 link	c.51_56delGCTGCT	p.Leu18_Leu19del	disruptive_inframe_deletion	Exon 2 of 14		NP_001161066.2	P10619-2B4E324X6R5C5
CTSA	NR_133656.2 link	n.96_101delGCTGCT		non_coding_transcript_exon_variant	Exon 2 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSA	ENST00000646241.3 link	c.51_56delGCTGCT	p.Leu18_Leu19del	disruptive_inframe_deletion	Exon 2 of 15		NM_000308.4	ENSP00000493613.2		P10619-1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000976

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000417

AC:

AN:

203638

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

112766

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000209

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000205

Gnomad SAS exome

AF:

0.0000377

Gnomad FIN exome

AF:

0.00218

Gnomad NFE exome

AF:

0.000372

Gnomad OTH exome

AF:

0.000392

GnomAD4 exome

AF:

0.0000737

AC:

100

AN:

1356660

Hom.:

AF XY:

0.0000696

AC XY:

AN XY:

674970

show subpopulations

Gnomad4 AFR exome

AF:

0.0000647

Gnomad4 AMR exome

AF:

0.0000744

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000381

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.0000376

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149832

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73032

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000976

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CTSA-related disorder

Benign:1

Jul 03, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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.

20-45891598-CCTGCTGCTGCTGCTGCTGCTGCTGCT-CCTGCTGCTGCTGCTGCTGCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over