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  3. TNRC6B
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Intellectual disability syndromic and non-syndromic

Gene: TNRC6B

Green List (high evidence)
TNRC6B (trinucleotide repeat containing 6B)
EnsemblGeneIds (GRCh38): ENSG00000100354
EnsemblGeneIds (GRCh37): ENSG00000100354
OMIM: 610740, Gene2Phenotype
TNRC6B is in 4 panels

2 reviews

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Granadillo et al (2020 - PMID: 32152250) report on 17 unrelated individuals with heterozygous TNRC6B variants.

Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.

Variable initial genetic tests (incl. karyotype, CMA, FMR1, sequencing of other genes) were normal in most individuals with 6/17 having additional variants, in (only) 2 cases contributing to the patient's phenotype.

Detected variants were identified following exome (14/17), targeted panel sequencing (2/17) or CMA (1/17) and included 14 pLoF, 1 missense SNV and 2 intragenic deletions.

Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype.

The protein encoded by TNRC6B (similar to TNRC6A, C) is involved in translational inhibition, through association with the Argonaute (Ago) family of proteins which are effectors of post-transcriptional gene silencing.

There were no variant studies performed.

Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism.

Animal models are not discussed (/possibly not available).

Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963).

A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).

Overall this gene can be upgraded to amber (ID is a feature although mild and not universal) or green rating (DD in all, >=4 subjects with ID and relevant variants). Please consider inclusion/upgrade in other relevant panels such as ASD.
Created: 6 May 2020, 3:35 p.m. | Last Modified: 6 May 2020, 3:35 p.m.
Panel Version: 0.2619

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay; Intellectual disability; Autistic behavior

Publications

Created: 6 May 2020, 3:35 p.m.
Last Modified: 6 May 2020, 3:35 p.m.
Panel version: 0.2619

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

No evidence currently for Mendelian disease association.
Created: 20 Nov 2019, 7:29 p.m. | Last Modified: 20 Nov 2019, 7:29 p.m.
Panel Version: 0.13

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Global developmental delay with speech and behavioural abnormalities, MIM# 619243

Created: 20 Nov 2019, 7:29 p.m.
Last Modified: 20 Nov 2019, 7:29 p.m.
Panel version: 0.3562

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genetic Health Queensland
  • Victorian Clinical Genetics Services
Phenotypes
  • Global developmental delay with speech and behavioural abnormalities, MIM# 619243
OMIM
610740
Clinvar variants
Variants in TNRC6B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Mar 2021, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TNRC6B were changed from Global developmental delay; Intellectual disability; Autistic behavior to Global developmental delay with speech and behavioural abnormalities, MIM# 619243

7 May 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behavior

7 May 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: TNRC6B were set to

7 May 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

7 May 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: tnrc6b has been classified as Green List (High Evidence).

11 Dec 2019, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: tnrc6b has been classified as Red List (Low Evidence).

10 Dec 2019, Gel status: 1

Entity classified by Genomics England curator

Chirag Patel (Genetic Health Queensland)

Gene: tnrc6b has been classified as Red List (Low Evidence).

22 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: TNRC6B was added gene: TNRC6B was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: TNRC6B was set to Unknown