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NM_000168.6(GLI3):c.2119C>T (p.Pro707Ser)

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Interpretation:
Uncertain significance​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Aug 20, 2021)
Last evaluated:
Jun 1, 2021
Accession:
VCV000013831.8
Variation ID:
13831
Description:
single nucleotide variant
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NM_000168.6(GLI3):c.2119C>T (p.Pro707Ser)

Allele ID
28870
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7p14.1
Genomic location
7: 41967908 (GRCh38) GRCh38 UCSC
7: 42007506 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P10071:p.Pro707Ser
NC_000007.13:g.42007506G>A
NC_000007.14:g.41967908G>A
... more HGVS
Protein change
P707S
Other names
-
Canonical SPDI
NC_000007.14:41967907:G:A
Functional consequence
functional variant [Sequence Ontology SO:0001536]
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00020
The Genome Aggregation Database (gnomAD) 0.00028
Trans-Omics for Precision Medicine (TOPMed) 0.00031
The Genome Aggregation Database (gnomAD), exomes 0.00027
Trans-Omics for Precision Medicine (TOPMed) 0.00029
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
The Genome Aggregation Database (gnomAD) 0.00019
Links
ClinGen: CA256987
UniProtKB: P10071#VAR_010055
OMIM: 165240.0019
dbSNP: rs121917716
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Dec 28, 2016 RCV000500441.2
Uncertain significance 1 criteria provided, single submitter Nov 19, 2018 RCV000542657.2
Uncertain significance 3 criteria provided, single submitter Jun 1, 2021 RCV000782254.5
Pathogenic 1 no assertion criteria provided Oct 1, 1997 RCV000014843.26
Likely pathogenic 1 no assertion criteria provided Nov 18, 2016 RCV000508658.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GLI3 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
638 665

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Dec 28, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Genetic Services Laboratory,University of Chicago
Accession: SCV000594998.1
Submitted: (Jul 05, 2017)
Evidence details
Uncertain significance
(Nov 19, 2018)
criteria provided, single submitter
Method: clinical testing
Pallister-Hall syndrome
Greig cephalopolysyndactyly syndrome
Allele origin: germline
Invitae
Accession: SCV000630786.2
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces proline with serine at codon 707 of the GLI3 protein (p.Pro707Ser). The proline residue is highly conserved and there is a … (more)
Uncertain significance
(Jun 01, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001800972.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
Identified in an individual with Greig cephalopolysyndactyly syndrome (GCPS) and individuals without GCPS in published literature (Wild et al., 1997; Sribudiani et al., 2018); also … (more)
Pathogenic
(Oct 01, 1997)
no assertion criteria provided
Method: literature only
GREIG CEPHALOPOLYSYNDACTYLY SYNDROME
Allele origin: germline
OMIM
Accession: SCV000035098.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Likely pathogenic
(Nov 18, 2016)
no assertion criteria provided
Method: clinical testing
Hirschsprung disease 1
(Oligogenic inheritance)
Allele origin: paternal
Clinical Genetics, Erasmus University Medical Center
Accession: SCV000328910.1
Submitted: (Nov 21, 2016)
Evidence details
Likely benign
(Sep 16, 2018)
no assertion criteria provided
Method: research
not provided
Allele origin: germline
Gharavi Laboratory,Columbia University
Accession: SCV000920747.1
Submitted: (Mar 05, 2019)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001548767.1
Submitted: (Mar 31, 2021)
Evidence details
Comment:
The GLI3 p.Pro707Ser variant was identified in the literature in one of two patients with Greig cephalopolysyndactyly syndrome (Wild_1997_PMID:9302279). The variant was identified in dbSNP … (more)

Functional evidence

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Functional consequence Method Result Submitter Supporting information
has functional consequence
Clinical Genetics, Erasmus University Medical Center
Accession: SCV000328910.1
Submitted: (Nov 21, 2016)
Evidence details

Citations for this variant

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Title Author Journal Year Link
Point mutations in GLI3 lead to misregulation of its subcellular localization. Krauss S PloS one 2009 PMID: 19829694
Point mutations in human GLI3 cause Greig syndrome. Wild A Human molecular genetics 1997 PMID: 9302279

Text-mined citations for rs121917716...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021