Intellectual disability
Gene: H3F3A

H3F3A (H3 histone family member 3A)
EnsemblGeneIds (GRCh38): ENSG00000163041
EnsemblGeneIds (GRCh37): ENSG00000163041
OMIM: 601128, Gene2Phenotype
H3F3A is in 6 panels

4 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.

Panel Version: 3.1510

Created: 9 Mar 2022, 3:40 p.m.
Last Modified: 9 Mar 2022, 3:40 p.m.
Panel version: 3.1510

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Upgraded from Red to Amber, but there is sufficient evidence to promoted to Green at the next GMS panel update (added 'for-review' tag).

Multiple unrelated cases (>30) with GDD/ID associated with de novo variants in this gene.
Created: 22 Dec 2020, 4:26 p.m. | Last Modified: 22 Dec 2020, 4:26 p.m.

Panel Version: 3.670

Currently not associated with any phenotype in OMIM, but is listed in Gene2Phenotype with a 'confirmed' disease confidence rating for 'Craniofacial with neurodevelopment disorders'.

- PMID: 31942419 (2019) - De novo missense variant identified by trio exome sequencing in a girl with secondary microcephaly, severe DD and ID, growth retardation and dysmorphic features. Brain MRI demonstrated hypoplasia of corpus callosum and cerebellum as well as thin layer of frontal and parietal periventricular gliosis. No functional analyses of the variant or patient cells were performed.

- PMID: 33268356 (2020) - De novo missense variants identified in 33 unrelated individuals with a shared phenotype of GDD/ID, usually severe and often progressive, with mostly minor congenital anomalies. 23/28 patients showed abnormalities on brain MRI including hypoplasia/agenesis of the corpus collosum (9), cortical atrophy (6) and impaired myelination (5). Variable seizure phenotypes were reported in 17/33 cases, all early-onset where specified, mostly during infancy (latest onset at 14 years of age).
Created: 22 Dec 2020, 4:20 p.m. | Last Modified: 22 Dec 2020, 4:20 p.m.

Panel Version: 3.669

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental delay; Neurodegeneration; Epilepsy; Facial dysmorphism; Congenital anomalies

Publications

Created: 22 Dec 2020, 4:20 p.m.
Last Modified: 22 Dec 2020, 4:20 p.m.
Panel version: 3.669

Zornitza Stark (Australian Genomics)

Green List (high evidence)

33 unrelated individuals reported with missense variants in H3F3A. Phenotype primarily comprised intellectual disability and minor congenital anomalies, regression in significant proportion. Seizures in 50%.
Created: 9 Dec 2020, 7:31 a.m. | Last Modified: 9 Dec 2020, 7:31 a.m.

Panel Version: 3.644

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability; regression; seizures

Publications

33268356

Created: 9 Dec 2020, 7:31 a.m.
Last Modified: 9 Dec 2020, 7:31 a.m.
Panel version: 3.644

Louise Daugherty (Genomics England Curator)

Added new-gene-name tag, new approved HGNC gene symbol for H3F3A is H3-3A
Created: 6 Sep 2019, 3:43 p.m. | Last Modified: 6 Sep 2019, 3:43 p.m.

Panel Version: 2.1022

Created: 6 Sep 2019, 3:43 p.m.
Last Modified: 6 Sep 2019, 3:43 p.m.
Panel version: 2.1022

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Victorian Clinical Genetics Services

Phenotypes

Developmental delay
Intellectual disability
Neurodegeneration
Epilepsy
Facial dysmorphism
Congenital anomalies

Tags

new-gene-name

OMIM

601128

Clinvar variants

Variants in H3F3A

Penetrance

None

Publications

Panels with this gene