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

Clinical significance:Uncertain significance (Last evaluated: Nov 19, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000542657.2

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)

Name:
Greig cephalopolysyndactyly syndrome (GCPS)
Synonyms:
Greig syndrome; Polysyndactyly with peculiar skull shape
Identifiers:
MONDO: MONDO:0008287; MedGen: C0265306; Orphanet: 380; OMIM: 175700
Name:
Pallister-Hall syndrome (PHS)
Synonyms:
Hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly
Identifiers:
MONDO: MONDO:0007804; MedGen: C0265220; Orphanet: 672; OMIM: 146510

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000630786Invitaecriteria provided, single submitter
Uncertain significance
(Nov 19, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Point mutations in GLI3 lead to misregulation of its subcellular localization.

Krauss S, So J, Hambrock M, Köhler A, Kunath M, Scharff C, Wessling M, Grzeschik KH, Schneider R, Schweiger S.

PLoS One. 2009 Oct 15;4(10):e7471. doi: 10.1371/journal.pone.0007471.

PubMed [citation]
PMID:
19829694
PMCID:
PMC2758996

Point mutations in human GLI3 cause Greig syndrome.

Wild A, Kalff-Suske M, Vortkamp A, Bornholdt D, König R, Grzeschik KH.

Hum Mol Genet. 1997 Oct;6(11):1979-84.

PubMed [citation]
PMID:
9302279
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000630786.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

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 moderate physicochemical difference between proline and serine. This variant is present in population databases (rs121917716, ExAC 0.03%). This variant has been reported in an individual affected with Greig syndrome (PMID: 9302279). ClinVar contains an entry for this variant (Variation ID: 13831). An experimental study has shown that this missense change partially disrupts the nuclear localization of GLI3 and reduces its transcriptional activity in a reporter assay (PMID: 19829694). In summary, this variant is a rare missense change that partially disrupts protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 30, 2021

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