ClinVar Genomic variation as it relates to human health
NM_032634.4(PIGO):c.3118G>A (p.Val1040Ile)
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.
Uncertain significance(4); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_032634.4(PIGO):c.3118G>A (p.Val1040Ile)
Variation ID: 366753 Accession: VCV000366753.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p13.3 9: 35089402 (GRCh38) [ NCBI UCSC ] 9: 35089399 (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 Dec 6, 2016 Feb 20, 2024 Dec 27, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032634.4:c.3118G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_116023.2:p.Val1040Ile missense NM_001201484.2:c.1867G>A NP_001188413.1:p.Val623Ile missense NM_152850.4:c.1867G>A NP_690577.2:p.Val623Ile missense NC_000009.12:g.35089402C>T NC_000009.11:g.35089399C>T NG_031990.1:g.12200G>A - Protein change
- V1040I, V623I
- Other names
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- Canonical SPDI
- NC_000009.12:35089401:C:T
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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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00020
Exome Aggregation Consortium (ExAC) 0.00025
The Genome Aggregation Database (gnomAD), exomes 0.00036
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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PIGO | - | - |
GRCh38 GRCh37 |
925 | 1004 |
Conditions - Germline
Condition
Help
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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Likely benign (1) |
criteria provided, single submitter
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Jan 14, 2021 | RCV000421736.12 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Dec 27, 2023 | RCV001080844.22 | |
PIGO-related disorder
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Uncertain significance (1) |
criteria provided, single submitter
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Oct 13, 2022 | RCV003392220.4 |
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
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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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Uncertain significance
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000479866.3
First in ClinVar: Dec 06, 2016 Last updated: Aug 20, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Likely benign
(Jan 14, 2021)
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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: SCV000514119.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as … (more)
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
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Uncertain significance
(May 07, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 2
Affected status: unknown
Allele origin:
germline
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New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV001431201.3 First in ClinVar: Sep 05, 2020 Last updated: Mar 05, 2022 |
Observation 1:
Clinical Features:
Seizure (present) , Intellectual disability (present)
Secondary finding: no
Observation 2:
Clinical Features:
Seizure (present) , Generalized non-motor (absence) seizure (present)
Secondary finding: no
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Likely benign
(Dec 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 2
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000652698.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
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Uncertain significance
(Jan 24, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hyperphosphatasia with intellectual disability syndrome 2
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Division Of Personalized Genomic Medicine, Columbia University Irving Medical Center
Accession: SCV004037344.1
First in ClinVar: Sep 30, 2023 Last updated: Sep 30, 2023 |
Comment:
The c.3118G>A variant in the PIGO gene is missense variant, which results in the substitution of a conserved valine residue at amino acid position 1040 … (more)
The c.3118G>A variant in the PIGO gene is missense variant, which results in the substitution of a conserved valine residue at amino acid position 1040 for an isoleucine (NP_116023.2). This variant localizes to coding exon 10 of the PIGO gene (11 coding exons in total; NM_032634.4). In silico predictors for this variant are not consistent: It is predicted to be neutral to protein structure and/or function by PROVEAN, but is predicted to be damaging by SIFT. This variant was reported in Genome Aggregation Database (gnomAD) with an allelic frequency of 0.0325% (92 out of 282,864 alleles). This variant is reported in ClinVar with three submissions of conflicting interpretation of pathogenicity, with two laboratories classifying it as a variant of uncertain clinical significance and one variant classifying it as likely benign (Variation ID# 366753). To the best of our knowledge, this specific variant has not been reported in the literature. Given this evidence, the c.3118G>A, p.Val1040Ile variant in PIGO is considered a variant of uncertain clinical significance. Parental studies were not conducted at our laboratory, but this variant was reported to be paternally inherited at another laboratory in a separate pregnancy of same parents (2019). (less)
Clinical Features:
Orofacial cleft (present)
Ethnicity/Population group: Hispanic American
Geographic origin: Spain
Tissue: DNA from products of conception
Comment on evidence:
Observed in trans with c.1723T>G
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Uncertain significance
(Oct 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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PIGO-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004119466.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The PIGO c.3118G>A variant is predicted to result in the amino acid substitution p.Val1040Ile. To our knowledge, this variant has not been reported in the … (more)
The PIGO c.3118G>A variant is predicted to result in the amino acid substitution p.Val1040Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.65% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-35089399-C-T), which is likely too frequent for a pathogenic variant. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs149439295 ...
HelpRecord last updated Sep 29, 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.