ClinVar Genomic variation as it relates to human health
NM_033419.5(PGAP3):c.850C>T (p.His284Tyr)
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_033419.5(PGAP3):c.850C>T (p.His284Tyr)
Variation ID: 800935 Accession: VCV000800935.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q12 17: 39673100 (GRCh38) [ NCBI UCSC ] 17: 37829353 (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 4, 2020 Apr 6, 2024 Mar 17, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_033419.5:c.850C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_219487.3:p.His284Tyr missense NM_001291726.2:c.697C>T NP_001278655.1:p.His233Tyr missense NM_001291728.2:c.787C>T NP_001278657.1:p.His263Tyr missense NM_001291730.2:c.558-234C>T intron variant NM_001291732.2:c.495-234C>T intron variant NM_001291733.2:c.433-234C>T intron variant NC_000017.11:g.39673100G>A NC_000017.10:g.37829353G>A NG_034125.1:g.19971C>T - Protein change
- H284Y, H263Y, H233Y
- Other names
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- Canonical SPDI
- NC_000017.11:39673099:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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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- Links
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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| PGAP3 | - | - |
GRCh38 GRCh37 |
188 | 202 | |
Conditions - Germline
| Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
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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| Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Mar 17, 2024 | RCV000985140.16 |
Submissions - Germline
| Classification
Help
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
(-)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 4
Affected status: yes
Allele origin:
germline
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Centogene AG - the Rare Disease Company
Accession: SCV001426548.1
First in ClinVar: Aug 09, 2020 Last updated: Aug 09, 2020 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 4
Affected status: yes
Allele origin:
germline
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Pathology and Clinical Laboratory Medicine, King Fahad Medical City
Accession: SCV001438826.1
First in ClinVar: Oct 25, 2020 Last updated: Oct 25, 2020 |
Number of individuals with the variant: 1
Ethnicity/Population group: Arab
Geographic origin: Middle East
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Pathogenic
(May 05, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 4
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001521056.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Pathogenic
(Apr 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 4
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003822830.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Mar 17, 2024)
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criteria provided, single submitter
Method: research
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Hyperphosphatasia with intellectual disability syndrome 4
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004804684.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
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Likely pathogenic
(Sep 26, 2019)
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no assertion criteria provided
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 4
Affected status: yes
Allele origin:
germline
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Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001133129.1
First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020 |
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Pathogenic
(Nov 07, 2022)
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no assertion criteria provided
Method: literature only
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HYPERPHOSPHATASIA WITH IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME 4
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV001244224.3
First in ClinVar: Apr 24, 2020 Last updated: Nov 13, 2022 |
Comment on evidence:
In 9 patients from 5 Saudi families with hyperphosphatasia with impaired intellectual development syndrome-4 (HPMRS4; 615716), Maddirevula et al. (2018) identified homozygosity for a founder … (more)
In 9 patients from 5 Saudi families with hyperphosphatasia with impaired intellectual development syndrome-4 (HPMRS4; 615716), Maddirevula et al. (2018) identified homozygosity for a founder c.850C-T transition (c.850C-T, NM_033419.3) in the PGAP3 gene that resulted in a histidine-to-tyrosine substitution at codon 284 (H284Y). This variant was absent from the gnomAD database on April 14, 2020 (Hamosh, 2020). In 4 patients from 2 consanguineous Saudi families with HPMRS4, Balobaid et al. (2018) identified homozygosity for the H284Y mutation in the PGAP3 gene. The authors proposed that this mutation might represent a founder mutation warranting targeted genetic testing once clinical suspicion of HPMRS4 is raised. (less)
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Pathogenic
(Apr 01, 2023)
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no assertion criteria provided
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 4
Affected status: yes
Allele origin:
germline
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Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)
Accession: SCV003927909.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
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Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort. | Bertoli-Avella AM | European journal of human genetics : EJHG | 2021 | PMID: 32860008 |
| Delineating the phenotypic spectrum of hyperphosphatasia with mental retardation syndrome 4 in 14 patients of Middle-Eastern origin. | Balobaid A | American journal of medical genetics. Part A | 2018 | PMID: 30345601 |
| Expanding the phenome and variome of skeletal dysplasia. | Maddirevula S | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29620724 |
| Hamosh, A. Personal Communication. 2020. Baltimore, Md. | - | - | - | - |
Text-mined citations for rs759541820 ...
HelpRecord last updated Aug 04, 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.