ClinVar Genomic variation as it relates to human health
NM_138387.4(G6PC3):c.210del (p.Phe71fs)
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_138387.4(G6PC3):c.210del (p.Phe71fs)
Variation ID: 189782 Accession: VCV000189782.13
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 44071175 (GRCh38) [ NCBI UCSC ] 17: 42148543 (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 Oct 5, 2015 Feb 14, 2024 Jan 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_138387.4:c.210del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_612396.1:p.Phe71fs frameshift NM_001319945.2:c.210del NP_001306874.1:p.Phe71fs frameshift NM_001384165.1:c.-195del 5 prime UTR NM_001384166.1:c.-330del 5 prime UTR NM_001384167.1:c.-320del 5 prime UTR NM_001384168.1:c.-311-453del intron variant NM_138387.3:c.210delC NC_000017.11:g.44071175del NC_000017.10:g.42148543del NG_015818.1:g.5446del LRG_182:g.5446del - Protein change
- F71fs
- Other names
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- Canonical SPDI
- NC_000017.11:44071174:C:
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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.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00011
Exome Aggregation Consortium (ExAC) 0.00018
1000 Genomes Project 30x 0.00031
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
Help
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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G6PC3 | - | - |
GRCh38 GRCh37 |
321 | 399 | |
LOC130060959 | - | - | - | GRCh38 | - | 74 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jan 24, 2024 | RCV000192088.13 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 8, 2023 | RCV003151753.1 |
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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Pathogenic
(Mar 08, 2023)
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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: SCV003840655.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
Frameshift 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; This … (more)
Frameshift 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; This variant is associated with the following publications: (PMID: 19775295, 27577878, 22050868, 34964150) (less)
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Pathogenic
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV003842046.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.011%). This variant was predicted to result in … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.011%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. It has been reported at least twice as pathogenic without evidence for the classification (PMID: 19775295). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Intellectual disability (present) , Ptosis (present) , Short stature (present) , Microcephaly (present) , Inguinal hernia (present) , Cryptorchidism (present) , Mitral regurgitation (present) , … (more)
Intellectual disability (present) , Ptosis (present) , Short stature (present) , Microcephaly (present) , Inguinal hernia (present) , Cryptorchidism (present) , Mitral regurgitation (present) , Atrial septal defect (present) , Abnormality of pulmonary circulation (present) (less)
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Pathogenic
(Jan 24, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000960122.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Phe71Serfs*46) in the G6PC3 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Phe71Serfs*46) in the G6PC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in G6PC3 are known to be pathogenic (PMID: 19118303, 25491320). This variant is present in population databases (rs769441127, gnomAD 0.08%). This premature translational stop signal has been observed in individual(s) with congenital neutropenia (PMID: 19775295, 22050868, 27577878). This variant is also known as I70fsX115 and Ile70fsX46. ClinVar contains an entry for this variant (Variation ID: 189782). For these reasons, this variant has been classified as Pathogenic. (less)
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not provided
(-)
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no classification provided
Method: literature only
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Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000222644.2
First in ClinVar: Oct 05, 2015 Last updated: Oct 01, 2022 |
Ethnicity/Population group: Hispanic
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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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Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. | Stray-Pedersen A | The Journal of allergy and clinical immunology | 2017 | PMID: 27577878 |
G6PC3 Deficiency. | Adam MP | - | 2015 | PMID: 25879134 |
Clinical spectrum and long-term follow-up of 14 cases with G6PC3 mutations from the French Severe Congenital Neutropenia Registry. | Desplantes C | Orphanet journal of rare diseases | 2014 | PMID: 25491320 |
A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations. | Banka S | Orphanet journal of rare diseases | 2013 | PMID: 23758768 |
Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 deficiency: novel genotypes and phenotypic variability in severe congenital neutropenia. | Boztug K | The Journal of pediatrics | 2012 | PMID: 22050868 |
Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia. | Xia J | British journal of haematology | 2009 | PMID: 19775295 |
A syndrome with congenital neutropenia and mutations in G6PC3. | Boztug K | The New England journal of medicine | 2009 | PMID: 19118303 |
Text-mined citations for rs769441127 ...
HelpRecord last updated Feb 20, 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.