ClinVar Genomic variation as it relates to human health
NM_001127178.3(PIGG):c.1163G>A (p.Trp388Ter)
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_001127178.3(PIGG):c.1163G>A (p.Trp388Ter)
Variation ID: 620287 Accession: VCV000620287.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4p16.3 4: 521104 (GRCh38) [ NCBI UCSC ] 4: 514893 (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 Mar 19, 2019 Feb 20, 2024 Jan 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001127178.3:c.1163G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001120650.1:p.Trp388Ter nonsense NM_001289051.2:c.896G>A NP_001275980.1:p.Trp299Ter nonsense NM_001289052.2:c.764G>A NP_001275981.1:p.Trp255Ter nonsense NM_001289053.2:c.896G>A NP_001275982.1:p.Trp299Ter nonsense NM_001289055.2:c.797G>A NP_001275984.1:p.Trp266Ter nonsense NM_001289057.2:c.848-556G>A intron variant NM_001345986.2:c.896G>A NP_001332915.1:p.Trp299Ter nonsense NM_001345987.2:c.896G>A NP_001332916.1:p.Trp299Ter nonsense NM_001345988.2:c.134G>A NP_001332917.1:p.Trp45Ter nonsense NM_001345989.2:c.1163G>A NP_001332918.1:p.Trp388Ter nonsense NM_001345990.2:c.-325G>A 5 prime UTR NM_001345991.2:c.-325G>A 5 prime UTR NM_001345994.2:c.89G>A NP_001332923.1:p.Trp30Ter nonsense NM_017733.5:c.1163G>A NP_060203.3:p.Trp388Ter nonsense NR_110293.2:n.1289G>A non-coding transcript variant NR_144326.2:n.1525G>A non-coding transcript variant NR_144327.2:n.1289G>A non-coding transcript variant NR_144328.2:n.1289G>A non-coding transcript variant NR_144329.2:n.1525G>A non-coding transcript variant NR_144330.2:n.1289G>A non-coding transcript variant NR_144331.2:n.1525G>A non-coding transcript variant NR_144332.2:n.1289G>A non-coding transcript variant NR_144333.2:n.1289G>A non-coding transcript variant NR_144334.2:n.1525G>A non-coding transcript variant NC_000004.12:g.521104G>A NC_000004.11:g.514893G>A NG_051621.1:g.26905G>A - Protein change
- W388*, W255*, W45*, W266*, W299*, W30*
- Other names
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- Canonical SPDI
- NC_000004.12:521103: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
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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PIGG | - | - |
GRCh38 GRCh37 |
988 | 1158 |
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
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 (2) |
criteria provided, multiple submitters, no conflicts
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Oct 23, 2020 | RCV000760651.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 14, 2023 | RCV002533843.2 |
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
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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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Pathogenic
(Jul 23, 2018)
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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: SCV000890543.1
First in ClinVar: Mar 19, 2019 Last updated: Mar 19, 2019 |
Comment:
The W388X variant in the PIGG gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This … (more)
The W388X variant in the PIGG gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W388X variant is not observed in large population cohorts (Lek et al., 2016). (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447097.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Seizure (present) , Cerebellar atrophy (present) , Muscle weakness (present) , Gait ataxia (present) , Polyneuropathy (present)
Sex: male
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Pathogenic
(Jan 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal recessive 53
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003223886.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 620287). This variant has not been reported in the literature in individuals affected with PIGG-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp388*) in the PIGG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIGG are known to be pathogenic (PMID: 26996948, 28581210, 28771251). (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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Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. | Lionel AC | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 28771251 |
Reduced cell surface levels of GPI-linked markers in a new case with PIGG loss of function. | Zhao JJ | Human mutation | 2017 | PMID: 28581210 |
Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia. | Makrythanasis P | American journal of human genetics | 2016 | PMID: 26996948 |
Text-mined citations for rs1560330387 ...
HelpRecord last updated Feb 28, 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.