NM_032861.4(SERAC1):c.438del (p.Thr147fs) AND 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Mar 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000850598.7

Allele description [Variation Report for NM_032861.4(SERAC1):c.438del (p.Thr147fs)]

NM_032861.4(SERAC1):c.438del (p.Thr147fs)

Gene:

SERAC1:serine active site containing 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6q25.3

Genomic location:

Preferred name:

NM_032861.4(SERAC1):c.438del (p.Thr147fs)

HGVS:

NC_000006.12:g.158146832del
NG_032889.1:g.26450del
NM_032861.4:c.438delMANE SELECT
NP_116250.3:p.Thr147fs
NC_000006.11:g.158567864del
NC_000006.11:g.158567864delG
NM_032861.3:c.438del
NM_032861.4:c.438del
NM_032861.4:c.438delCMANE SELECT
NR_073096.2:n.562del

Protein change:

T147fs

Links:

OMIM: 614725.0010; dbSNP: rs1583595091

NCBI 1000 Genomes Browser:

rs1583595091

Molecular consequence:

NM_032861.4:c.438del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_073096.2:n.562del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

protein truncation [Variation Ontology: 0015]

Observations:

Condition(s)

Name:: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL)
Synonyms:: 3-METHYLGLUTACONIC ACIDURIA, TYPE VI; MEGDEL syndrome
Identifiers:: MONDO: MONDO:0013875; MedGen: C4040739; Orphanet: 352328; OMIM: 614739

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Homo sapiens EEF1A lysine methyltransferase 1 (EEF1AKMT1), transcript variant 1,...
Homo sapiens EEF1A lysine methyltransferase 1 (EEF1AKMT1), transcript variant 1, mRNA
gi|974576760|ref|NM_174928.2|

Nucleotide
H2AC15 H2A clustered histone 15 [Homo sapiens]
H2AC15 H2A clustered histone 15 [Homo sapiens]
Gene ID:8330

Gene
Gene Links for GEO Profiles (Select 34531091) (1)
Gene
c-MYC depletion effect on carcinoma cell lines
c-MYC depletion effect on carcinoma cell lines
Accession: GDS2526

GEO DataSets
Related DataSets for GEO Profiles (Select 34526442) (1)
GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000992825	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 31, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24997715, 25741868
SCV001132994	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Pathogenic (Aug 25, 2019)	germline	clinical testing
SCV001334139	Ro'ya Specialized Medical Laboratories, King Abdulaziz University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 31, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002016242	OMIM	no assertion criteria provided	Pathogenic (Nov 17, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002555220	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004806153	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 25, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Arab	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The Expanding MEGDEL Phenotype: Optic Nerve Atrophy, Microcephaly, and Myoclonic Epilepsy in a Child with SERAC1 Mutations.

Lumish HS, Yang Y, Xia F, Wilson A, Chung WK.

JIMD Rep. 2014;16:75-9. doi: 10.1007/8904_2014_322. Epub 2014 Jul 6.

PubMed [citation]

PMID:: 24997715
PMCID:: PMC4221303

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Baylor Genetics, SCV000992825.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV001132994.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ro'ya Specialized Medical Laboratories, King Abdulaziz University, SCV001334139.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Arab	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From OMIM, SCV002016242.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For description of the 1-bp deletion (c.438delC) in the SERAC1 gene, predicted to result in a frameshift and premature termination (Thr147fsTer22), that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL; 614739) by Lumish et al. (2014), see 614725.0001.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002555220.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004806153.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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