NM_000308.4(CTSA):c.248A>G (p.Asn83Ser) AND Combined deficiency of sialidase AND beta galactosidase

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 30, 2022
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:: RCV001899639.3

Allele description [Variation Report for NM_000308.4(CTSA):c.248A>G (p.Asn83Ser)]

NM_000308.4(CTSA):c.248A>G (p.Asn83Ser)

Gene:

CTSA:cathepsin A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_000308.4(CTSA):c.248A>G (p.Asn83Ser)

HGVS:

NC_000020.11:g.45891969A>G
NG_008291.1:g.6018A>G
NG_033108.1:g.4319T>C
NM_000308.4:c.248A>GMANE SELECT
NM_001127695.3:c.248A>G
NM_001167594.3:c.248A>G
NP_000299.3:p.Asn83Ser
NP_001121167.1:p.Asn83Ser
NP_001161066.2:p.Asn83Ser
NC_000020.10:g.44520608A>G
NR_133656.2:n.293A>G

Protein change:

N83S

Links:

dbSNP: rs758876717

NCBI 1000 Genomes Browser:

rs758876717

Molecular consequence:

NM_000308.4:c.248A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127695.3:c.248A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001167594.3:c.248A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_133656.2:n.293A>G - 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
SCV002145433	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 30, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002145433

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 30, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002145433.2

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

Description

This sequence change replaces asparagine with serine at codon 101 of the CTSA protein (p.Asn101Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs758876717, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CTSA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1371708). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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.

#	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: Sep 29, 2024

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