NM_032861.4(SERAC1):c.391T>C (p.Cys131Arg) AND 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 19, 2022
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:: RCV001314802.8

Allele description [Variation Report for NM_032861.4(SERAC1):c.391T>C (p.Cys131Arg)]

NM_032861.4(SERAC1):c.391T>C (p.Cys131Arg)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

6q25.3

Genomic location:

Preferred name:

NM_032861.4(SERAC1):c.391T>C (p.Cys131Arg)

Other names:

p.C131R:TGT>CGT

HGVS:

NC_000006.12:g.158146878A>G
NG_032889.1:g.26403T>C
NM_032861.4:c.391T>CMANE SELECT
NP_116250.3:p.Cys131Arg
NC_000006.11:g.158567910A>G
NM_032861.3:c.391T>C
NR_073096.2:n.515T>C

Protein change:

C131R

Links:

dbSNP: rs147085187

NCBI 1000 Genomes Browser:

rs147085187

Molecular consequence:

NM_032861.4:c.391T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_073096.2:n.515T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

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Conus cervus 16S ribosomal RNA gene, partial sequence; mitochondrial
Conus cervus 16S ribosomal RNA gene, partial sequence; mitochondrial
gi|269308819|gb|FJ868142.1|

Nucleotide
Homo sapiens WD repeat containing planar cell polarity effector (WDPCP), RefSeqG...
Homo sapiens WD repeat containing planar cell polarity effector (WDPCP), RefSeqGene on chromosome 2
gi|1245838175|ref|NG_028144.2|

Nucleotide
SRP224947 (16)
SRA
serine palmitoyltransferase 2 isoform X1 [Homo sapiens]
serine palmitoyltransferase 2 isoform X1 [Homo sapiens]
gi|767982054|ref|XP_011535686.1|

Protein
Focal non-motor seizure
Focal non-motor seizure

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001505350	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002555242	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001505350

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002555242

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 15, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001505350.3

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

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 131 of the SERAC1 protein (p.Cys131Arg). This variant is present in population databases (rs147085187, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SERAC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 215150). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Genome-Nilou Lab, SCV002555242.1

#	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

Last Updated: Oct 20, 2024

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