ClinVar Genomic variation as it relates to human health
NM_152419.3(HGSNAT):c.1360C>T (p.Gln454Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_152419.3(HGSNAT):c.1360C>T (p.Gln454Ter)
Variation ID: 374408 Accession: VCV000374408.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8p11.21 8: 43192413 (GRCh38) [ NCBI UCSC ] 8: 43047556 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 15, 2017 Feb 28, 2024 Jun 30, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152419.3:c.1360C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689632.2:p.Gln454Ter nonsense NM_001363227.2:c.1360C>T NP_001350156.1:p.Gln454Ter nonsense NM_001363228.2:c.1168C>T NP_001350157.1:p.Gln390Ter nonsense NM_001363229.2:c.496C>T NP_001350158.1:p.Gln166Ter nonsense NC_000008.11:g.43192413C>T NC_000008.10:g.43047556C>T NG_009552.1:g.56965C>T - Protein change
- Q454*, Q390*, Q166*
- Other names
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- Canonical SPDI
- NC_000008.11:43192412:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- protein truncation Variation Ontology [VariO:0015]
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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HGSNAT | - | - |
GRCh38 GRCh37 |
1056 | 1245 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely pathogenic (2) |
criteria provided, single submitter
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Oct 16, 2017 | RCV000415469.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 30, 2023 | RCV002521465.2 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Oct 16, 2017)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis, MPS-III-C
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000794741.1
First in ClinVar: Jan 15, 2017 Last updated: Jan 15, 2017 |
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Pathogenic
(Jun 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 73
Mucopolysaccharidosis, MPS-III-C
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003440195.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024 |
Comment:
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, … (more)
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. ClinVar contains an entry for this variant (Variation ID: 374408). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 27733599). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln454*) in the HGSNAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). (less)
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Pathogenic
(Mar 01, 2016)
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no assertion criteria provided
Method: research
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Mucopolysaccharidosis, MPS-III-C
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
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GENETICS INSTITUTE, National university of Colombia
Accession: SCV000323116.1
First in ClinVar: Jan 15, 2017 Last updated: Jan 15, 2017 |
Comment:
As a result of genetic community visits in Boyacá, two patients with a phenotype compatible with MPS III in the village of Runta, adjacent to … (more)
As a result of genetic community visits in Boyacá, two patients with a phenotype compatible with MPS III in the village of Runta, adjacent to the city of Tunja rural area were identified. The research group Clinical Genetics at the National University of Colombia visited this place, leading to the identification of three more patients with the same presentation. In the first two cases identified, enzymatic assays for MPS III A and III B with negative results. Considering that MPS IIID is much less common, we considered MPS IIIC as a higher probability, so that the complete sequence of the gene HGSNAT, which revealed homozygous state, a new causal mutation was obtained. Mutation analysis in the remaining patients confirmed that all harboring the same mutation also in the homozygous state. All patients had coarse features that had become evident around 12 to 18 months and facial hirsutism. Hirsutism body was present in 80% of patients. Three patients had painful contractures of the large joints (hip, elbow and knee), as well as claw hand deformity. All patients had multiple disostosis and cranial hyperostosis and two patients had kyphosis. In all patients expressive language delay was presented, none of the patients becomes normal language for their chronological age, inattentiveness, echolalia and anxiety is evident. (less)
Number of individuals with the variant: 5
Clinical Features:
Coarse facial features (present) , Macrocephaly (present) , Facial hirsutism (present) , Hurler syndrome (present) , Cranial hyperostosis (present) , Delayed speech and language development … (more)
Coarse facial features (present) , Macrocephaly (present) , Facial hirsutism (present) , Hurler syndrome (present) , Cranial hyperostosis (present) , Delayed speech and language development (present) , Hyperactivity (present) , Aggressive behavior (present) , Echolalia (present) (less)
Age: 5-16 years
Sex: mixed
Geographic origin: Colombia
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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protein truncation
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GENETICS INSTITUTE, National university of Colombia
Accession: SCV000323116.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Natural History of Sanfilippo Syndrome Type C in Boyacá, Colombia. | Velasco HM | Journal of child neurology | 2017 | PMID: 27733599 |
Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene. | Feldhammer M | Human mutation | 2009 | PMID: 19479962 |
Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome). | Hrebícek M | American journal of human genetics | 2006 | PMID: 17033958 |
Text-mined citations for rs1057518644 ...
HelpRecord last updated Mar 05, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.