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Intellectual disability

Gene: TMEM94

Green List (high evidence)
TMEM94 (transmembrane protein 94)
EnsemblGeneIds (GRCh38): ENSG00000177728
EnsemblGeneIds (GRCh37): ENSG00000177728
TMEM94 is in 3 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: TMEM94 was added to the ID panel by Konstantinos Varvagiannis, and rated Amber. Stephen et al., 2018 (PMID:30526868) identified biallelic (homozygous or compound het) variants in 10 patients from 6 unrelated families of different ethnic origins. All affected individuals manifested with delays in development and dysmorphic facial features. All variants were predicted to be truncating variants. There is a question from Konstantinos over whether the phenotypes fall under the scope of the ID panel since the authors refer to ID in the abstract, and speech delay, motor delay and learning disability in Table 1. Global developmental delay is reported for individual II.1 in Family 1, gross developmental delay is reported in Family 3, mild DD and an IQ of 58 is reported for individual II.2 in Family 5, and developmental delay was reported for Individual II.2 in Family 6. TMEM94 has now also been associated with a disorder in OMIM: Intellectual developmental disorder with cardiac defects and dysmorphic facies, 618316. Therefore on balance and because of sufficient numbers of general DD reported in PMID:30526868, I have included TMEM94 on the ID panel as a Green gene.
Created: 14 May 2019, 10:42 a.m.
Created: 14 May 2019, 10:42 a.m.

Panel version: 2.816

Konstantinos Varvagiannis (Other)

I don't know

Stephen et al. (https://doi.org/10.1016/j.ajhg.2018.11.001) report on 10 individuals from 6 unrelated families with bi-allelic truncating TMEM94 variants. The common phenotype consisted of global DD/ID, similar facial features as well as the presence of congenital heart defects (in all but one).

Speech as well as motor delay and learning difficulties were universal features. ID is mentioned in the abstract, explicitly specified for one individual and implied for some of the rest.

Overall 6 different LoF variants are reported. Reduced expression was demonstrated while gene expression microarray and RNA sequencing expression studies demonstrated dysregulation of several essential genes. Using a CRISPR/Cas9 mouse model loss of Tmem94 was shown to be embryonically lethal with craniofacial, cardiac anomalies as well as abnormal neuronal migration pattern observed in homozygous mutant mice embryos.

TMEM94 is not associated with any phenotype in G2P nor in OMIM.

As a result this gene can be considered for inclusion in this panel probably as amber (or green).
Sources: Literature
Created: 10 Dec 2018, 3:29 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Global developmental delay; Intellectual disability; Abnormal heart morphology; Abnormality of head or neck

Created: 10 Dec 2018, 3:29 p.m.

Panel version: 2.579

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Intellectual developmental disorder with cardiac defects and dysmorphic facies, OMIM:618316
Clinvar variants
Variants in TMEM94
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

20 Mar 2026, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag gene-checked was removed from gene: TMEM94.

3 Oct 2024, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TMEM94 were changed from Intellectual developmental disorder with cardiac defects and dysmorphic facies, 618316; Global developmental delay; Intellectual disability; Abnormal heart morphology; Abnormality of head or neck to Intellectual developmental disorder with cardiac defects and dysmorphic facies, OMIM:618316

8 May 2022, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag gene-checked tag was added to gene: TMEM94.

14 May 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: tmem94 has been classified as Green List (High Evidence).

13 May 2019, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: TMEM94 were changed from Global developmental delay; Intellectual disability; Abnormal heart morphology; Abnormality of head or neck to Intellectual developmental disorder with cardiac defects and dysmorphic facies, 618316; Global developmental delay; Intellectual disability; Abnormal heart morphology; Abnormality of head or neck

13 May 2019, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: TMEM94 were set to

10 Dec 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: TMEM94 was added gene: TMEM94 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TMEM94 were set to Global developmental delay; Intellectual disability; Abnormal heart morphology; Abnormality of head or neck Penetrance for gene: TMEM94 were set to Complete Review for gene: TMEM94 was set to AMBER