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Intellectual disability

Gene: GTF3C3

Amber List (moderate evidence)

GTF3C3 (general transcription factor IIIC subunit 3)
EnsemblGeneIds (GRCh38): ENSG00000119041
EnsemblGeneIds (GRCh37): ENSG00000119041
OMIM: 604888, Gene2Phenotype
GTF3C3 is in 1 panel

3 reviews

Catherine Snow (Genomics England)

I don't know

Three unrelated individuals with variants in GTF3C3 all reported to have ID.
PMID: 30552426 reported on a patient with epilepsy and intellectual disability.
PMID: 28940097 reported on an individual who had a homozygous splice site variant which was shown to cause skipping of exon 10 and parts of exon 11 (in-frame deletion) in a patient with profound microcephaly, characteristic facial appearance and failure to thrive.
PMID: 28097321 reported on a homozygous missense variant in GTF3C3 in two affected sisters with a phenotype including mild ID, seizures and dysmorphisms and classified it as a moderately confident candidate gene.
GTF3C3 has no disease gene phenotype associations in OMIM or Gene2Phenotype and limited clinical information is provided on the degree of ID. All the cases identified have variable phenotype in terms of skeletal features and epilepsy. Therefore GTF3C3 will remain as Amber and be added to the watchlist.
Created: 29 Jul 2019, 1:41 p.m. | Last Modified: 29 Jul 2019, 1:41 p.m.
Panel Version: 2.989

Konstantinos Varvagiannis (Other)

I don't know

Papuc et al. (PMID: 30552426) report on one further patient with epilepsy and intellectual disability (all participants of the study had moderate to profound ID) due to biallelic GTF3C3 mutations.

This individual had the following variants (NM_012086.4): c.2419C>T / p.(Arg807Cys) and c.503C>T / p.(Ala168Val). A healthy sister of the proband was heterozygous for the first variant but not the second one. The first variant affects only 1 (of 2) Refseq isoforms while the second affects both. Both variants were predicted pathogenic in silico and absent from ExAC.

The phenotype of previously published individuals (from PMIDs 28940097, 28097321) is briefly summarized. According to the authors, Tcf4 - a yeast ortholog of GTF3C3 - has been shown to interact with BRF1 for regulation of RNA polymerase III-mediated transcription. Arguments are provided for phenotypic similarities to the BRF1-related phenotype, cerebellofaciodental syndrome (MIM 616202).

The gene is not associated with any phenotype in OMIM, nor in G2P. It is not included in gene panels for ID offered by diagnostic laboratories.

As a result it could be considered for upgrade probably to amber (or green).
Created: 19 Dec 2018, 11:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Global developmental delay; Intellectual disability; Seizures

Publications

Zornitza Stark (Australian Genomics)

I don't know

Two unrelated families with bi-allelic variants in this gene, ID is part of the phenotype. Consider inclusion as Amber.
Created: 22 Jun 2018, 11:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Global developmental delay
  • Intellectual disability
  • Seizures
Tags
watchlist
OMIM
604888
Clinvar variants
Variants in GTF3C3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Jul 2019, Gel status: 2

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: gtf3c3 has been classified as Amber List (Moderate Evidence).

29 Jul 2019, Gel status: 1

Added Tag

Catherine Snow (Genomics England)

Tag watchlist tag was added to gene: GTF3C3.

29 Jul 2019, Gel status: 1

Set Phenotypes

Catherine Snow (Genomics England)

Phenotypes for gene: GTF3C3 were changed from to Global developmental delay; Intellectual disability; Seizures

29 Jul 2019, Gel status: 1

Set publications

Catherine Snow (Genomics England)

Publications for gene: GTF3C3 were set to 28940097, 28097321

28 Sep 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to GTF3C3.

22 Jun 2018, Gel status: 0

Added New Source

Zornitza Stark (Australian Genomics)

GTF3C3 was added to Intellectual disability panel. Sources: Literature

22 Jun 2018, Gel status: 0

Created

Zornitza Stark (Australian Genomics)

GTF3C3 was created by Zornitza Stark