NM_000199.5(SGSH):c.817G>A (p.Asp273Asn) AND Mucopolysaccharidosis, MPS-III-A

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Jan 4, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000199.5(SGSH):c.817G>A (p.Asp273Asn)]

NM_000199.5(SGSH):c.817G>A (p.Asp273Asn)

SGSH:N-sulfoglucosamine sulfohydrolase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000199.5(SGSH):c.817G>A (p.Asp273Asn)
  • NC_000017.11:g.80212203C>T
  • NG_008229.1:g.13198G>A
  • NM_000199.5:c.817G>AMANE SELECT
  • NM_001352921.2:c.817G>A
  • NM_001352922.2:c.817G>A
  • NP_000190.1:p.Asp273Asn
  • NP_001339850.1:p.Asp273Asn
  • NP_001339851.1:p.Asp273Asn
  • NC_000017.10:g.78186002C>T
  • NM_000199.3:c.817G>A
  • NR_148201.2:n.731G>A
Protein change:
dbSNP: rs1046551417
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000199.5:c.817G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352921.2:c.817G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352922.2:c.817G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148201.2:n.731G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Mucopolysaccharidosis, MPS-III-A (MPS3A)
SULFAMIDASE DEFICIENCY; Mucopoly-saccharidosis type 3A; Sanfilippo syndrome A; See all synonyms [MedGen]
MONDO: MONDO:0009655; MedGen: C0086647; Orphanet: 581; Orphanet: 79269; OMIM: 252900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000793588Counsylcriteria provided, single submitter
Uncertain significance
(Aug 22, 2017)
unknownclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV000947471Invitaecriteria provided, single submitter
(Jan 4, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing



Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece.

Héron B, Mikaeloff Y, Froissart R, Caridade G, Maire I, Caillaud C, Levade T, Chabrol B, Feillet F, Ogier H, Valayannopoulos V, Michelakakis H, Zafeiriou D, Lavery L, Wraith E, Danos O, Heard JM, Tardieu M.

Am J Med Genet A. 2011 Jan;155A(1):58-68. doi: 10.1002/ajmg.a.33779.

PubMed [citation]

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA.

Sidhu NS, Schreiber K, Pröpper K, Becker S, Usón I, Sheldrick GM, Gärtner J, Krätzner R, Steinfeld R.

Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1321-35. doi: 10.1107/S1399004714002739. Epub 2014 Apr 30.

PubMed [citation]
See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000793588.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000947471.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change replaces aspartic acid with asparagine at codon 273 of the SGSH protein (p.Asp273Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another SGSH variant in individuals affected with mucopolysaccharidosis type III (PMID: 11182930, 27590925, Invitae). ClinVar contains an entry for this variant (Variation ID: 553454). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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