ClinVar Genomic variation as it relates to human health
NM_022356.4(P3H1):c.838C>T (p.Gln280Ter)
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_022356.4(P3H1):c.838C>T (p.Gln280Ter)
Variation ID: 1076376 Accession: VCV001076376.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.2 1: 42758954 (GRCh38) [ NCBI UCSC ] 1: 43224625 (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 May 10, 2021 Feb 14, 2024 Jan 30, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_022356.4:c.838C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_071751.3:p.Gln280Ter nonsense NM_001146289.2:c.838C>T NP_001139761.1:p.Gln280Ter nonsense NM_001243246.2:c.838C>T NP_001230175.1:p.Gln280Ter nonsense NM_022356.3:c.838C>T NC_000001.11:g.42758954G>A NC_000001.10:g.43224625G>A NG_008123.1:g.13131C>T LRG_5:g.13131C>T - Protein change
- Q280*
- Other names
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- Canonical SPDI
- NC_000001.11:42758953: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
Help
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
Help
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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P3H1 | - | - |
GRCh38 GRCh37 |
828 | 861 |
Conditions - Germline
Condition
Help
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
Help
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 (4) |
criteria provided, multiple submitters, no conflicts
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Jan 30, 2024 | RCV001390265.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 16, 2022 | RCV003154031.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 15, 2022 | RCV003394025.4 |
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
Help
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
Help
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 the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Osteogenesis imperfecta type 8
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002517838.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Nov 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Osteogenesis imperfecta type 8
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002588763.1
First in ClinVar: Nov 05, 2022 Last updated: Nov 05, 2022 |
Comment:
The c.838C>T;p.(Gln280*) variant creates a premature translational stop signal in the P3H1 gene. It is expected to result in an absent or disrupted protein product … (more)
The c.838C>T;p.(Gln280*) variant creates a premature translational stop signal in the P3H1 gene. It is expected to result in an absent or disrupted protein product - PVS1. ClinVar contains an entry for this variant (ClinVar ID: 1076376) - PS4_supporting. This variant is not present in population databases (rs1652551021, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Brazil
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Pathogenic
(Sep 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV003842861.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24498616, 23301918) (less)
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Pathogenic
(Sep 15, 2022)
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criteria provided, single submitter
Method: clinical testing
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P3H1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004119412.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The P3H1 c.838C>T variant is predicted to result in premature protein termination (p.Gln280*). This variant in the compound heterozygous condition along with P3H1 c.1080+1G>T variant … (more)
The P3H1 c.838C>T variant is predicted to result in premature protein termination (p.Gln280*). This variant in the compound heterozygous condition along with P3H1 c.1080+1G>T variant was reported in one patient with osteogenesis imperfecta (Pepin et al 2013. PubMed ID: 24498616). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in P3H1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Osteogenesis imperfecta type 8
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004178063.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Jan 30, 2024)
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criteria provided, single submitter
Method: clinical testing
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Osteogenesis imperfecta type 8
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001591942.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln280*) in the P3H1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln280*) in the P3H1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in P3H1 are known to be pathogenic (PMID: 17277775, 18566967, 19088120, 22281939). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive osteogenesis imperfecta (PMID: 24498616). ClinVar contains an entry for this variant (Variation ID: 1076376). For these reasons, this variant has been classified as Pathogenic. (less)
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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
HelpTitle | Author | Journal | Year | Link |
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Allelic background of LEPRE1 mutations that cause recessive forms of osteogenesis imperfecta in different populations. | Pepin MG | Molecular genetics & genomic medicine | 2013 | PMID: 24498616 |
A founder mutation in LEPRE1 carried by 1.5% of West Africans and 0.4% of African Americans causes lethal recessive osteogenesis imperfecta. | Cabral WA | Genetics in medicine : official journal of the American College of Medical Genetics | 2012 | PMID: 22281939 |
Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation. | Willaert A | Journal of medical genetics | 2009 | PMID: 19088120 |
CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. | Baldridge D | Human mutation | 2008 | PMID: 18566967 |
Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. | Cabral WA | Nature genetics | 2007 | PMID: 17277775 |
Text-mined citations for rs1652551021 ...
HelpRecord last updated Mar 11, 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.