NM_000199.5(SGSH):c.506+1G>A AND Mucopolysaccharidosis, MPS-III-A

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Nov 8, 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:: RCV001942694.8

Allele description [Variation Report for NM_000199.5(SGSH):c.506+1G>A]

NM_000199.5(SGSH):c.506+1G>A

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.506+1G>A

HGVS:

NC_000017.11:g.80214614C>T
NG_008229.1:g.10787G>A
NG_008229.2:g.10719G>A
NM_000199.5:c.506+1G>AMANE SELECT
NM_001352921.3:c.506+1G>A
NM_001352922.2:c.506+1G>A
NC_000017.10:g.78188413C>T

Links:

dbSNP: rs763063355

NCBI 1000 Genomes Browser:

rs763063355

Molecular consequence:

NM_000199.5:c.506+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001352921.3:c.506+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001352922.2:c.506+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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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nssv677810 (0)
SRA
NADH-plastoquinone oxidoreductase subunit 5 (plastid) [Drypetes lateriflora]
NADH-plastoquinone oxidoreductase subunit 5 (plastid) [Drypetes lateriflora]
gi|1942106641|ref|YP_009975430.1|

Protein
NADH-plastoquinone oxidoreductase subunit 4 (chloroplast) [Lycoris aurea]
NADH-plastoquinone oxidoreductase subunit 4 (chloroplast) [Lycoris aurea]
gi|1832108168|gb|QJA15329.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002136031	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 8, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 11182930, 21204211, 22976768, 28492532
SCV002812123	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 4, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004201093	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 17, 2023)	unknown	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

SCV002136031

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 8, 2023)

germline

clinical testing

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

SCV002812123

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 4, 2022)

unknown

clinical testing

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

SCV004201093

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 17, 2023)

unknown

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Mutational analysis of Sanfilippo syndrome type A (MPS IIIA): identification of 13 novel mutations.

Beesley CE, Young EP, Vellodi A, Winchester BG.

J Med Genet. 2000 Sep;37(9):704-7. No abstract available.

PubMed [citation]

PMID:: 11182930
PMCID:: PMC1734705

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002136031.3

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

Description

This sequence change affects a donor splice site in intron 4 of the SGSH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SGSH are known to be pathogenic (PMID: 11182930, 21204211, 22976768). This variant is present in population databases (rs763063355, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with mucopolysaccharidosis type IIIA (Invitae). ClinVar contains an entry for this variant (Variation ID: 1365580). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 Fulgent Genetics, Fulgent Genetics, SCV002812123.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004201093.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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