NM_000512.5(GALNS):c.331C>T (p.Gln111Ter) AND Mucopolysaccharidosis, MPS-IV-A

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 9, 2023
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:: RCV000690516.13

Allele description [Variation Report for NM_000512.5(GALNS):c.331C>T (p.Gln111Ter)]

NM_000512.5(GALNS):c.331C>T (p.Gln111Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000512.5(GALNS):c.331C>T (p.Gln111Ter)

HGVS:

NC_000016.10:g.88841083G>A
NG_008667.1:g.20884C>T
NM_000512.5:c.331C>TMANE SELECT
NM_001323543.2:c.-225C>T
NM_001323544.2:c.349C>T
NP_000503.1:p.Gln111Ter
NP_001310473.1:p.Gln117Ter
NC_000016.9:g.88907491G>A
NM_000512.4:c.331C>T

Protein change:

Q111*

Links:

dbSNP: rs200374326

NCBI 1000 Genomes Browser:

rs200374326

Molecular consequence:

NM_001323543.2:c.-225C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000512.5:c.331C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323544.2:c.349C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000818203	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 9, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12442278, 9375852, 28492532
SCV001547663	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2021)	germline	research	PubMed (5) [See all records that cite these PMIDs] 16287098, 24726177, 32905071, 34387910, 25741868
SCV002045031	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	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

SCV000818203

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 9, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001547663

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2021)

germline

research

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

SCV002045031

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 7, 2021)

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	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular analysis of Turkish mucopolysaccharidosis IVA (Morquio A) patients: identification of novel mutations in the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene.

Terzioglu M, Tokatli A, Coskun T, Emre S.

Hum Mutat. 2002 Dec;20(6):477-8.

PubMed [citation]

PMID:: 12442278

Fourteen novel mucopolysaccharidosis IVA producing mutations in GALNS gene.

Tomatsu S, Fukuda S, Cooper A, Wraith JE, Ferreira P, Di Natale P, Tortora P, Fujimoto A, Kato Z, Yamada N, Isogai K, Yamagishi A, Sukegawa K, Suzuki Y, Shimozawa N, Kondo N, Sly WS, Orii T.

Hum Mutat. 1997;10(5):368-75.

PubMed [citation]

PMID:: 9375852

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000818203.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln111*) in the GALNS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALNS are known to be pathogenic (PMID: 12442278). This variant is present in population databases (rs200374326, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type IV (PMID: 9375852). ClinVar contains an entry for this variant (Variation ID: 569803). For these reasons, this variant has been 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

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV001547663.3

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

Description

Nonsense variant (PVS1_very strong); in vitro functional studies supportive of a damaging effect on the gene product (low in vitro enzymatic activity; PS3_supporting); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); very low frequency in gnomAD v2.1.1 (PM2_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 Genome-Nilou Lab, SCV002045031.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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