NM_000168.6(GLI3):c.2119C>T (p.Pro707Ser) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Jun 1, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000782254.5

Allele description [Variation Report for NM_000168.6(GLI3):c.2119C>T (p.Pro707Ser)]

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

Gene:
GLI3:GLI family zinc finger 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p14.1
Genomic location:
Preferred name:
NM_000168.6(GLI3):c.2119C>T (p.Pro707Ser)
HGVS:
  • NC_000007.14:g.41967908G>A
  • NG_008434.1:g.274113C>T
  • NM_000168.6:c.2119C>TMANE SELECT
  • NP_000159.3:p.Pro707Ser
  • NC_000007.13:g.42007506G>A
  • NM_000168.5:c.2119C>T
  • P10071:p.Pro707Ser
Protein change:
P707S; PRO707SER
Links:
UniProtKB: P10071#VAR_010055; OMIM: 165240.0019; dbSNP: rs121917716
NCBI 1000 Genomes Browser:
rs121917716
Molecular consequence:
  • NM_000168.6:c.2119C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
functional variant [Sequence Ontology: SO:0001536]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000920747Gharavi Laboratory,Columbia Universityno assertion criteria provided
Likely benign
(Sep 16, 2018)
germlineresearch

PubMed (1)
[See all records that cite this PMID]

SCV001548767Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedUncertain significanceunknownclinical testing

SCV001800972GeneDxcriteria provided, single submitter
Uncertain significance
(Jun 1, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedresearch
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Gharavi Laboratory,Columbia University, SCV000920747.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001548767.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 (ID: rs121917716), ClinVar (classified as a VUS by Invitae and Genetic Services Laboratory at University of Chicago, as likely pathogenic by Clinical Genetics at Erasmus University Medical Center and as likely benign by Gharavi Laboratory at Columbia University), Cosmic (FATHMM prediction: pathogenic; score=0.97) and LOVD 3.0 (classified as a VUS, likely pathogenic and pathogenic). The variant was also identified in control databases in 73 of 282622 chromosomes at a frequency of 0.000258 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 65 of 128924 chromosomes (freq: 0.000504), Other in 2 of 7228 chromosomes (freq: 0.000277), Latino in 5 of 35440 chromosomes (freq: 0.000141) and African in 1 of 24970 chromosomes (freq: 0.00004), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish) or South Asian populations. The p.Pro707 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001800972.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 observed in heterozygous state in several clinically unaffected individuals referred for genetic testing at GeneDx; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 27535533, 9302279, 10441570, 10441342, 29601828, 19829694)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

Support Center