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Intellectual disability syndromic and non-syndromic

Gene: EMC1

Green List (high evidence)

EMC1 (ER membrane protein complex subunit 1)
EnsemblGeneIds (GRCh38): ENSG00000127463
EnsemblGeneIds (GRCh37): ENSG00000127463
OMIM: 616846, Gene2Phenotype
EMC1 is in 5 panels

3 reviews

Chern Lim (Victorian Clinical Genetics Services)

Three additional cases with monoallelic inheritance in PMID: 35234901 , patients have developmental delay, truncal hypotonia, seizures and cortical visual impairment.

So far, there are 4 cases of monoallelic inheritance: 3 de novo (PMIDs: 26942288, 35234901) and one likely post-zygotic mosaicism (PMID: 35234901 - variant was absent in mother, father not tested).

All four of these are missense (Gly471Arg, Pro582His, Pro582Arg, Pro584His) and are located in the middle region of the protein, while the AR missense variants are on either ends of the protein.
Created: 9 Aug 2023, 4:01 a.m. | Last Modified: 9 Aug 2023, 4:01 a.m.
Panel Version: 0.5324

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

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

Achchuthan Shanmugasundram (Genomics England)

Green List (high evidence)

Chung et al 2022 (PMID: 35234901) report 3 unrelated children with severe to profound developmental delay, truncal hypotonia, seizures and cortical visual impairment. A c.1745C > A; p.Pro582His (de novo) variant in EMC1 was found in 2 of the individuals. The other child had EMC1 c.1745C > G; p.Pro582Arg (mosaic; not inherited from mother, father deceased). Variants were identified by WES and confirmed by Sanger sequencing. In a Drosophila model the identified variants didn't rescue the lethality of a null allele. They also found variations in dosage of the wild-type EMC1, specifically in glia, lead to pupal lethality.

As there are three additional unrelated cases of monoallelic variants in patients with an intellectual disability phenotype reported now, the mode of inheritance should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'
Created: 1 Mar 2023, 2:35 p.m. | Last Modified: 1 Mar 2023, 2:35 p.m.
Panel Version: 0.5179

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Four unrelated families with bi-allelic variants in this gene reported. Single individual with heterozygous variant: insufficient evidence at present for mono allelic variants causing disease.
Sources: Expert list
Created: 2 Feb 2020, 4:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM# 616875

Publications

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

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM# 616875
OMIM
616846
Clinvar variants
Variants in EMC1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

10 Aug 2023, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: EMC1 were set to 26942288; 29271071

10 Aug 2023, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

2 Feb 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: emc1 has been classified as Green List (High Evidence).

2 Feb 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: emc1 has been classified as Green List (High Evidence).

2 Feb 2020, Gel status: 1

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: EMC1 was added gene: EMC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list Mode of inheritance for gene: EMC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EMC1 were set to 26942288; 29271071 Phenotypes for gene: EMC1 were set to Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM# 616875 Review for gene: EMC1 was set to GREEN gene: EMC1 was marked as current diagnostic