NC_000006.11:g.(?_158532398)_(162868359_?)del AND 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 29, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003122912.1

Allele description

NC_000006.11:g.(?_158532398)_(162868359_?)del

Genes:

AGPAT4:1-acylglycerol-3-phosphate O-acyltransferase 4 [Gene - OMIM - HGNC]
MAS1:MAS1 proto-oncogene, G protein-coupled receptor [Gene - OMIM - HGNC]
PNLDC1:PARN like ribonuclease domain containing exonuclease 1 [Gene - OMIM - HGNC]
TAGAP:T cell activation RhoGTPase activating protein [Gene - OMIM - HGNC]
TULP4:TUB like protein 4 [Gene - OMIM - HGNC]
WTAP:WT1 associated protein [Gene - OMIM - HGNC]
ACAT2:acetyl-CoA acetyltransferase 2 [Gene - OMIM - HGNC]
AIRN:antisense of IGF2R non-protein coding RNA [Gene - OMIM - HGNC]
DYNLT1:dynein light chain Tctex-type 1 [Gene - OMIM - HGNC]
EZR:ezrin [Gene - OMIM - HGNC]
FNDC1:fibronectin type III domain containing 1 [Gene - OMIM - HGNC]
GTF2H5:general transcription factor IIH subunit 5 [Gene - OMIM - HGNC]
IGF2R:insulin like growth factor 2 receptor [Gene - OMIM - HGNC]
LPA:lipoprotein(a) [Gene - OMIM - HGNC]
LINC02901:long intergenic non-protein coding RNA 2901 [Gene - HGNC]
MRPL18:mitochondrial ribosomal protein L18 [Gene - OMIM - HGNC]
MAP3K4:mitogen-activated protein kinase kinase kinase 4 [Gene - OMIM - HGNC]
PRKN:parkin RBR E3 ubiquitin protein ligase [Gene - OMIM - HGNC]
PLG:plasminogen [Gene - OMIM - HGNC]
RSPH3:radial spoke head 3 [Gene - OMIM - HGNC]
SERAC1:serine active site containing 1 [Gene - OMIM - HGNC]
SLC22A1:solute carrier family 22 member 1 [Gene - OMIM - HGNC]
SLC22A2:solute carrier family 22 member 2 [Gene - OMIM - HGNC]
SLC22A3:solute carrier family 22 member 3 [Gene - OMIM - HGNC]
SOD2:superoxide dismutase 2 [Gene - OMIM - HGNC]
SYTL3:synaptotagmin like 3 [Gene - HGNC]
TCP1:t-complex 1 [Gene - OMIM - HGNC]
TMEM181:transmembrane protein 181 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6q25.3-26

Genomic location:

Chr6: 158532398 - 162868359 (on Assembly GRCh37)

Preferred name:

NC_000006.11:g.(?_158532398)_(162868359_?)del

HGVS:

NC_000006.11:g.(?_158532398)_(162868359_?)del

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003795778	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22683713, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003795778

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 29, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.

Wortmann SB, Vaz FM, Gardeitchik T, Vissers LE, Renkema GH, Schuurs-Hoeijmakers JH, Kulik W, Lammens M, Christin C, Kluijtmans LA, Rodenburg RJ, Nijtmans LG, Grünewald A, Klein C, Gerhold JM, Kozicz T, van Hasselt PM, Harakalova M, Kloosterman W, Barić I, Pronicka E, Ucar SK, et al.

Nat Genet. 2012 Jun 10;44(7):797-802. doi: 10.1038/ng.2325.

PubMed [citation]

PMID:: 22683713

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

Details of each submission

From Invitae, SCV003795778.1

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

Description

A gross deletion of the genomic region encompassing the full coding sequence of the SERAC1 gene has been identified. Loss-of-function variants in SERAC1 are known to be pathogenic (PMID: 22683713). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with SERAC1-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	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: Jul 29, 2023

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