NM_000512.5(GALNS):c.841_867del (p.Thr281_Asn289del) AND Mucopolysaccharidosis, MPS-IV-A

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 12, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001578523.7

Allele description [Variation Report for NM_000512.5(GALNS):c.841_867del (p.Thr281_Asn289del)]

NM_000512.5(GALNS):c.841_867del (p.Thr281_Asn289del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000512.5(GALNS):c.841_867del (p.Thr281_Asn289del)

HGVS:

NC_000016.10:g.88835252_88835278del
NG_008667.1:g.26697_26723del
NM_000512.5:c.841_867delMANE SELECT
NM_001323543.2:c.286_312del
NM_001323544.2:c.859_885del
NP_000503.1:p.Thr281_Asn289del
NP_001310472.1:p.Thr96_Asn104del
NP_001310473.1:p.Thr287_Asn295del
NC_000016.9:g.88901652_88901678del
NC_000016.9:g.88901660_88901686del
NM_000512.5:c.841_867del27MANE SELECT

Links:

dbSNP: rs1567530426

NCBI 1000 Genomes Browser:

rs1567530426

Molecular consequence:

NM_000512.5:c.841_867del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001323543.2:c.286_312del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001323544.2:c.859_885del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-IV-A (MPS4A)
Synonyms:: MORQUIO SYNDROME A; GALACTOSAMINE-6-SULFATASE DEFICIENCY; GALNS DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009659; MedGen: C0086651; Orphanet: 309297; Orphanet: 582; OMIM: 253000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001547805	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2021)	germline	curation	PubMed (8) [See all records that cite these PMIDs] 16287098, 24726177, 32993725, 7633425, 8844220, 9298823, 34387910, 25741868
SCV004535389	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 6, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15241807, 24875751, 29731656, 8844220, 32993725, 28492532
SCV005641479	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 12, 2024)	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

SCV001547805

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2021)

germline

curation

PubMed (8)
[See all records that cite these PMIDs]

SCV004535389

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 6, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV005641479

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 12, 2024)

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	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A).

Tomatsu S, Montaño AM, Nishioka T, Gutierrez MA, Peña OM, Tranda Firescu GG, Lopez P, Yamaguchi S, Noguchi A, Orii T.

Hum Mutat. 2005 Dec;26(6):500-12.

PubMed [citation]

PMID:: 16287098

Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

Morrone A, Tylee KL, Al-Sayed M, Brusius-Facchin AC, Caciotti A, Church HJ, Coll MJ, Davidson K, Fietz MJ, Gort L, Hegde M, Kubaski F, Lacerda L, Laranjeira F, Leistner-Segal S, Mooney S, Pajares S, Pollard L, Ribeiro I, Wang RY, Miller N.

Mol Genet Metab. 2014 Jun;112(2):160-70. doi: 10.1016/j.ymgme.2014.03.004. Epub 2014 Mar 20. Erratum in: Mol Genet Metab. 2014 Nov;113(3):237.

PubMed [citation]

PMID:: 24726177
PMCID:: PMC4203673

See all PubMed Citations (12)

Details of each submission

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV001547805.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (8)

Description

In vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); located in a mutational hot spot and/or critical and well-established functional domain without benign variation (PM1_moderate); absent from gnomAD v2.1.1 (PM2_moderate); protein length changes as a result of in-frame deletions in a nonrepeat region (PM4_moderate)

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004535389.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

ClinVar contains an entry for this variant (Variation ID: 1048421). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GALNS protein in which other variant(s) (p.Phe285del) have been determined to be pathogenic (PMID: 15241807, 24875751, 29731656). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has been observed in individual(s) with Morquio A syndrome (PMID: 8844220, 32993725). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant, c.841_867del, results in the deletion of 9 amino acid(s) of the GALNS protein (p.Thr281_Asn289del), but otherwise preserves the integrity of the reading frame.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV005641479.1

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

#	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: Apr 7, 2025

ClinVar

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