NM_000512.5(GALNS):c.1A>T (p.Met1Leu) AND Mucopolysaccharidosis, MPS-IV-A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 12, 2024
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:: RCV002002426.6

Allele description [Variation Report for NM_000512.5(GALNS):c.1A>T (p.Met1Leu)]

NM_000512.5(GALNS):c.1A>T (p.Met1Leu)

Genes:

LOC130059762:ATAC-STARR-seq lymphoblastoid silent region 7883 [Gene]
GALNS:galactosamine (N-acetyl)-6-sulfatase [Gene - OMIM - HGNC]
TRAPPC2L:trafficking protein particle complex subunit 2L [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000512.5(GALNS):c.1A>T (p.Met1Leu)

HGVS:

NC_000016.10:g.88856877T>A
NG_008667.1:g.5090A>T
NM_000512.5:c.1A>TMANE SELECT
NM_001323543.2:c.-431A>T
NM_001323544.2:c.-152A>T
NP_000503.1:p.Met1Leu
NC_000016.9:g.88923285T>A

Protein change:

M1L

Links:

dbSNP: rs771531650

NCBI 1000 Genomes Browser:

rs771531650

Molecular consequence:

NM_001323543.2:c.-431A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001323544.2:c.-152A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000512.5:c.1A>T - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000512.5:c.1A>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002228710	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 12, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15241807, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002228710

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 12, 2024)

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

Citations

PubMed

Mucopolysaccharidosis IVA (Morquio A): identification of novel common mutations in the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene in Italian patients.

Tomatsu S, Filocamo M, Orii KO, Sly WS, Gutierrez MA, Nishioka T, Serrato OP, Di Natale P, Montaño AM, Yamaguchi S, Kondo N, Orii T, Noguchi A.

Hum Mutat. 2004 Aug;24(2):187-8.

PubMed [citation]

PMID:: 15241807

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, SCV002228710.4

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

Description

This sequence change affects the initiator methionine of the GALNS mRNA. The next in-frame methionine is located at codon 22. This variant is present in population databases (rs771531650, gnomAD 0.005%). Disruption of the initiator codon has been observed in individual(s) with mucopolysaccharidosis IVA (PMID: 15241807). ClinVar contains an entry for this variant (Variation ID: 1453466). Studies have shown that disruption of the initiator codon alters GALNS gene expression (PMID: 15241807). 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

Last Updated: May 16, 2025

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