U.S. flag

An official website of the United States government

NM_032861.4(SERAC1):c.1684+2T>C AND 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 23, 2023
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:
RCV003646718.2

Allele description [Variation Report for NM_032861.4(SERAC1):c.1684+2T>C]

NM_032861.4(SERAC1):c.1684+2T>C

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.1684+2T>C
HGVS:
  • NC_000006.12:g.158114787A>G
  • NG_032889.1:g.58494T>C
  • NM_032861.4:c.1684+2T>CMANE SELECT
  • NC_000006.11:g.158535819A>G
  • NR_073096.2:n.1601T>C
Molecular consequence:
  • NR_073096.2:n.1601T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_032861.4:c.1684+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004466155Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 23, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

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
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004466155.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change affects a donor splice site in intron 15 of the SERAC1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SERAC1 are known to be pathogenic (PMID: 22683713). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SERAC1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024