NM_000199.5(SGSH):c.197C>G (p.Ser66Trp) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 19, 2021
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:: RCV002512807.2

Allele description [Variation Report for NM_000199.5(SGSH):c.197C>G (p.Ser66Trp)]

NM_000199.5(SGSH):c.197C>G (p.Ser66Trp)

Genes:

SLC26A11:solute carrier family 26 member 11 [Gene - OMIM - HGNC]
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.197C>G (p.Ser66Trp)

HGVS:

NC_000017.11:g.80217084G>C
NG_008229.1:g.8317C>G
NM_000199.5:c.197C>GMANE SELECT
NM_001352921.3:c.197C>G
NM_001352922.2:c.197C>G
NP_000190.1:p.Ser66Trp
NP_001339850.1:p.Ser66Trp
NP_001339851.1:p.Ser66Trp
NC_000017.10:g.78190883G>C
NM_000199.3:c.197C>G
NM_000199.4:c.197C>G
NR_148201.2:n.217C>G
P51688:p.Ser66Trp
p.S66W

Protein change:

S66W; SER66TRP

Links:

UniProtKB: P51688#VAR_007390; OMIM: 605270.0003; dbSNP: rs104894637

NCBI 1000 Genomes Browser:

rs104894637

Molecular consequence:

NM_000199.5:c.197C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352921.3:c.197C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001352922.2:c.197C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148201.2:n.217C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003565285	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 19, 2021)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 9158154, 9554748, 10601282, 21061399, 21910976, 24314109, 26787381, 29023963, 30809705 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003565285

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 19, 2021)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

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

Molecular defects in Sanfilippo syndrome type A.

Blanch L, Weber B, Guo XH, Scott HS, Hopwood JJ.

Hum Mol Genet. 1997 May;6(5):787-91.

PubMed [citation]

PMID:: 9158154

Identification of molecular defects in Italian Sanfilippo A patients including 13 novel mutations.

Di Natale P, Balzano N, Esposito S, Villani GR.

Hum Mutat. 1998;11(4):313-20.

PubMed [citation]

PMID:: 9554748

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV003565285.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The c.197C>G (p.S66W) alteration is located in exon 2 (coding exon 2) of the SGSH gene. This alteration results from a C to G substitution at nucleotide position 197, causing the serine (S) at amino acid position 66 to be replaced by a tryptophan (W). Based on data from the Genome Aggregation Database (gnomAD) database, the SGSH c.197C>G alteration was observed in 0.01% (23/257594) of total alleles studied, with a frequency of 0.02% (23/117902) in the European (non-Finnish) subpopulation. This mutation has been detected as heterozygous, compound heterozygous, and homozygous, in individuals with typical severe presentations of Mucopolysaccaridosis type IIIA (Sanfilippo syndrome type A) (Blanch, 1997; Di Natale, 1998; Valstar, 2010; Ouesleti, 2011; Delgadillo, 2013; Shapiro, 2016; Knottnerus, 2017; Zanetti, 2019). In addition, one functional study showed that this mutation results in a drastically reduced level of functional protein as well as lowered specific activity (Perkins, 1999). This amino acid position is highly conserved in available vertebrate species. The in silico prediction for the p.S66W alteration is inconclusive. Based on the available evidence, this alteration is 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 19, 2024

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