NM_000308.4(CTSA):c.60del (p.Ser21fs) AND Combined deficiency of sialidase AND beta galactosidase

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 6, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001420871.3

Allele description [Variation Report for NM_000308.4(CTSA):c.60del (p.Ser21fs)]

NM_000308.4(CTSA):c.60del (p.Ser21fs)

Genes:

LOC130065974:ATAC-STARR-seq lymphoblastoid active region 17954 [Gene]
CTSA:cathepsin A [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_000308.4(CTSA):c.60del (p.Ser21fs)

HGVS:

NC_000020.11:g.45891628del
NG_008291.1:g.5677del
NG_033108.1:g.4660del
NM_000308.4:c.60delMANE SELECT
NM_001127695.3:c.60del
NM_001167594.3:c.60del
NP_000299.3:p.Ser21fs
NP_001121167.1:p.Ser21fs
NP_001161066.2:p.Ser21fs
NC_000020.10:g.44520267del
NM_000308.3:c.114delG
NM_000308.4:c.60delGMANE SELECT
NR_133656.2:n.105del

Protein change:

S21fs

Links:

dbSNP: rs750928198

NCBI 1000 Genomes Browser:

rs750928198

Molecular consequence:

NM_000308.4:c.60del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127695.3:c.60del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167594.3:c.60del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_133656.2:n.105del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Combined deficiency of sialidase AND beta galactosidase (GSL)
Synonyms:: CATHEPSIN A DEFICIENCY; Galactosialidosis; Goldberg syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009737; MedGen: C0268233; Orphanet: 351; OMIM: 256540

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001623291	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Apr 6, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 28603679, 23915561, 15110321, 16538002, 32036093 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001623291

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Apr 6, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Galactosialidosis: historic aspects and overview of investigated and emerging treatment options.

Annunziata I, d'Azzo A.

Expert Opin Orphan Drugs. 2017;5(2):131-141. doi: 10.1080/21678707.2016.1266933. Epub 2016 Dec 14.

PubMed [citation]

PMID:: 28603679
PMCID:: PMC5461780

Galactosialidosis: review and analysis of CTSA gene mutations.

Caciotti A, Catarzi S, Tonin R, Lugli L, Perez CR, Michelakakis H, Mavridou I, Donati MA, Guerrini R, d'Azzo A, Morrone A.

Orphanet J Rare Dis. 2013 Aug 2;8:114. doi: 10.1186/1750-1172-8-114. Review.

PubMed [citation]

PMID:: 23915561
PMCID:: PMC3737020

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623291.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: CTSA c.60delG/p.Ser21ProfsX71 (also known as c.114delG/p.Ser39ProfsX71) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8.3e-06 in 242104 control chromosomes. c.60delG has been reported in the literature in homozygous and compound heterozygous individuals affected with Galactosialidosis (e.g. Malvagia_2004, Caciotti_2013). These data indicate that the variant is likely to be associated with disease. Several publications report a reduction in beta-galactosidase (GLB1) and neuramidase (NEU1) enzymatic acitvity in fibroblasts from patients with the variant (e.g.Malvagia_2004, Caciotti_2013). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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