NM_000308.4(CTSA):c.51_54delinsC (p.Leu19del) AND Combined deficiency of sialidase AND beta galactosidase

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 9, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000256455.8

Allele description [Variation Report for NM_000308.4(CTSA):c.51_54delinsC (p.Leu19del)]

NM_000308.4(CTSA):c.51_54delinsC (p.Leu19del)

Genes:

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

Variant type:

Indel

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_000308.4(CTSA):c.51_54delinsC (p.Leu19del)

Other names:

p.Leu37del

HGVS:

NC_000020.11:g.45891619_45891622delinsC
NG_008291.1:g.5668_5671delinsC
NG_033108.1:g.4666_4669delinsG
NM_000308.4:c.51_54delinsCMANE SELECT
NM_001127695.3:c.51_54delinsC
NM_001167594.3:c.51_54delinsC
NP_000299.3:p.Leu19del
NP_001121167.1:p.Leu19del
NP_001161066.2:p.Leu19del
NC_000020.10:g.44520258_44520261delinsC
NM_000308.2:c.105_108delGCTGinsC
NM_000308.2:c.105_108delinsC
NM_000308.3:c.105_108delGCTGinsC
NR_133656.2:n.96_99delinsC

Protein change:

L19del

Links:

dbSNP: rs886039898

NCBI 1000 Genomes Browser:

rs886039898

Molecular consequence:

NM_000308.4:c.51_54delinsC - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001127695.3:c.51_54delinsC - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001167594.3:c.51_54delinsC - inframe_deletion - [Sequence Ontology: SO:0001822]
NR_133656.2:n.96_99delinsC - 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
SCV000323195	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha	criteria provided, single submitter (HA_assertions_20161101)	Likely benign (Sep 14, 2017)	unknown	research	Citation Link,
SCV000825536	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28554332, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000323195

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha

criteria provided, single submitter

(HA_assertions_20161101)

Likely benign
(Sep 14, 2017)

unknown

research

Citation Link,

SCV000825536

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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
not provided	unknown	no	1	not provided	not provided	1	not provided	research

Citations

PubMed

Genomic diagnosis for children with intellectual disability and/or developmental delay.

Bowling KM, Thompson ML, Amaral MD, Finnila CR, Hiatt SM, Engel KL, Cochran JN, Brothers KB, East KM, Gray DE, Kelley WV, Lamb NE, Lose EJ, Rich CA, Simmons S, Whittle JS, Weaver BT, Nesmith AS, Myers RM, Barsh GS, Bebin EM, Cooper GM.

Genome Med. 2017 May 30;9(1):43. doi: 10.1186/s13073-017-0433-1.

PubMed [citation]

PMID:: 28554332
PMCID:: PMC5448144

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 HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - CSER-HudsonAlpha, SCV000323195.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	no	1	not provided	not provided		1	not provided	not provided	not provided

From Invitae, SCV000825536.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 558865). This variant has been observed in individual(s) with clinical features of galactosialidosis (PMID: 28554332). 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, c.105_108delinsC, is a complex sequence change that results in the deletion of 1 amino acid(s) in the CTSA protein (p.Leu37del).

#	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: Feb 28, 2024

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