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Intellectual disability

Gene: TNRC6B

Red List (low evidence)

TNRC6B (trinucleotide repeat containing 6B)
EnsemblGeneIds (GRCh38): ENSG00000100354
EnsemblGeneIds (GRCh37): ENSG00000100354
OMIM: 610740, Gene2Phenotype
TNRC6B is in 2 panels

1 review

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, 3:36 p.m. | Last Modified: 6 May 2020, 3:36 p.m.
Panel Version: 3.35

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

Global developmental delay; Intellectual disability; Autistic behavior



Clinvar variants
Variants in TNRC6B
Panels with this gene

History Filter Activity

29 Sep 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: TNRC6B was added gene: TNRC6B was added to Intellectual disability. Sources: Victorian Clinical Genetics Services Mode of inheritance for gene: TNRC6B was set to