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NM_000199.5(SGSH):c.673T>C (p.Phe225Leu) AND Mucopolysaccharidosis, MPS-III-A

Clinical significance:Pathogenic (Last evaluated: Nov 7, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000489872.4

Allele description [Variation Report for NM_000199.5(SGSH):c.673T>C (p.Phe225Leu)]

NM_000199.5(SGSH):c.673T>C (p.Phe225Leu)

Gene:
SGSH:N-sulfoglucosamine sulfohydrolase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q25.3
Genomic location:
Preferred name:
NM_000199.5(SGSH):c.673T>C (p.Phe225Leu)
HGVS:
  • NC_000017.11:g.80213876A>G
  • NG_008229.1:g.11525T>C
  • NM_000199.5:c.673T>CMANE SELECT
  • NM_001352921.3:c.673T>C
  • NM_001352922.2:c.673T>C
  • NP_000190.1:p.Phe225Leu
  • NP_001339850.1:p.Phe225Leu
  • NP_001339851.1:p.Phe225Leu
  • NC_000017.10:g.78187675A>G
  • NM_000199.3:c.673T>C
  • NR_148201.2:n.587T>C
Protein change:
F225L
Links:
dbSNP: rs1057521801
NCBI 1000 Genomes Browser:
rs1057521801
Molecular consequence:
  • NM_000199.5:c.673T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352921.3:c.673T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352922.2:c.673T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148201.2:n.587T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
4

Condition(s)

Name:
Mucopolysaccharidosis, MPS-III-A (MPS3A)
Synonyms:
SULFAMIDASE DEFICIENCY; Mucopoly-saccharidosis type 3A; Sanfilippo syndrome A; See all synonyms [MedGen]
Identifiers:
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)
OriginMethodCitations
SCV000575936Geisinger Autism and Developmental Medicine Institute,Geisinger Health Systemcriteria provided, single submitter
Pathogenic
(Apr 26, 2017)
maternalclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002045498Genome-Nilou Labcriteria provided, single submitter
Pathogenic
(Nov 7, 2021)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedmaternalyes4not providednot providednot providednot providedclinical testing

Citations

PubMed

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]
PMID:
21204211

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 Geisinger Autism and Developmental Medicine Institute,Geisinger Health System, SCV000575936.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (2)

Description

The following ACMG criteria are met: PS1 (Same amino acid change as pathogenic variant, Heron 2010), PS3 (Well-established functional study), PM2 (Absent from population databases), PM3 (In trans with pathogenic variant), PP1 (Co-segregation with disease in multiple family members). Two sisters in our clinical practice are compound heterozygotes for E355K and P225L and a clinical diagnosis of MPS IIIA was confirmed by clinical exam, positive urine screen, and absent enzyme activity in leukocytes. The younger sister has global developmental delays, autism spectrum disorder, sensorineural hearing loss, myopia, astigmatism, and a seizure disorder. The older sister has intellectual disability, autism spectrum disorder, sensorineural hearing loss, myopia, astigmatism, recurrent otitis media, precocious puberty, and seizure disorder.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalyesnot providednot providednot provided2not providednot providednot provided

From Genome-Nilou Lab, SCV002045498.1

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

Last Updated: Jul 8, 2022

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