NM_000512.5(GALNS):c.836ACA[1] (p.Asn280del) AND Mucopolysaccharidosis, MPS-IV-A

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 1, 2021
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:: RCV001093708.6

Allele description [Variation Report for NM_000512.5(GALNS):c.836ACA[1] (p.Asn280del)]

NM_000512.5(GALNS):c.836ACA[1] (p.Asn280del)

Gene:

GALNS:galactosamine (N-acetyl)-6-sulfatase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000512.5(GALNS):c.836ACA[1] (p.Asn280del)

HGVS:

NC_000016.10:g.88835270TGT[1]
NC_000016.10:g.88835270_88835272TGT[1]
NG_008667.1:g.26692ACA[1]
NM_000512.5:c.836ACA[1]MANE SELECT
NM_000512.5:c.839_841del
NM_001323543.2:c.281ACA[1]
NM_001323544.2:c.854ACA[1]
NP_000503.1:p.Asn280del
NP_001310472.1:p.Asn95del
NP_001310473.1:p.Asn286del
NC_000016.9:g.88901678TGT[1]
NM_000512.5:c.839_841delMANE SELECT
NM_000512.5:c.839_841delACAMANE SELECT
p.Asn280del

Protein change:

N280del

Links:

dbSNP: rs1389218771

NCBI 1000 Genomes Browser:

rs1389218771

Molecular consequence:

NM_000512.5:c.836ACA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001323543.2:c.281ACA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001323544.2:c.854ACA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Functional consequence:

Unknown function

Observations:

Condition(s)

Name:: Mucopolysaccharidosis, MPS-IV-A (MPS4A)
Synonyms:: MPS IVA; Morquio syndrome A; MPS 4A; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009659; MedGen: C0086651; Orphanet: 309297; Orphanet: 582; OMIM: 253000

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Mirror movements 1

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001190356	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001547804	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 1, 2021)	germline	research	PubMed (2) [See all records that cite these PMIDs] 34387910, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001190356

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

clinical testing

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

SCV001547804

Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 1, 2021)

germline

research

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	yes	not provided	not provided	not provided	not provided	not provided	research
Indian Hindu	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants.

Zanetti A, D'Avanzo F, AlSayed M, Brusius-Facchin AC, Chien YH, Giugliani R, Izzo E, Kasper DC, Lin HY, Lin SP, Pollard L, Singh A, Tonin R, Wood T, Morrone A, Tomanin R.

Hum Mutat. 2021 Nov;42(11):1384-1398. doi: 10.1002/humu.24270. Epub 2021 Aug 23. Review.

PubMed [citation]

PMID:: 34387910
PMCID:: PMC9291100

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV001190356.1

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

Description

A compound heterozygous deletion variation in exon 8 of the GALNS gene that results in the premature termination of the protein at codon 280 was detected. The observed variant c.839_841delACA (p.Asn280del) has not been reported in the 1000 genomes, gnomAD and ExAC databases. The in silico prediction of the variant is damaging by MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as likely pathogenic.

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

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV001547804.3

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

Description

Absent from gnomAD v2.1.1 (PM2_moderate); protein length changes as a result of in-frame deletions in a nonrepeat region (PM4_supporting)

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

Last Updated: Feb 4, 2024

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