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NM_001278716.2(FBXL4):c.1687C>T (p.Gln563Ter) AND Mitochondrial DNA depletion syndrome 13

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 10, 2017
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:
RCV000501548.2

Allele description [Variation Report for NM_001278716.2(FBXL4):c.1687C>T (p.Gln563Ter)]

NM_001278716.2(FBXL4):c.1687C>T (p.Gln563Ter)

Gene:
FBXL4:F-box and leucine rich repeat protein 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q16.1
Genomic location:
Preferred name:
NM_001278716.2(FBXL4):c.1687C>T (p.Gln563Ter)
HGVS:
  • NC_000006.12:g.98875430G>A
  • NG_033903.1:g.77577C>T
  • NM_001278716.2:c.1687C>TMANE SELECT
  • NM_012160.5:c.1687C>T
  • NP_001265645.1:p.Gln563Ter
  • NP_036292.2:p.Gln563Ter
  • NP_036292.2:p.Gln563Ter
  • NC_000006.11:g.99323306G>A
  • NM_012160.4:c.1687C>T
  • NR_103836.2:n.1672C>T
Protein change:
Q563*
Links:
dbSNP: rs1554215964
NCBI 1000 Genomes Browser:
rs1554215964
Molecular consequence:
  • NR_103836.2:n.1672C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001278716.2:c.1687C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012160.5:c.1687C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Mitochondrial DNA depletion syndrome 13
Synonyms:
Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type)
Identifiers:
MONDO: MONDO:0014198; MedGen: C3809592; Orphanet: 369897; OMIM: 615471

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000598189Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 10, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome.

Dai H, Zhang VW, El-Hattab AW, Ficicioglu C, Shinawi M, Lines M, Schulze A, McNutt M, Gotway G, Tian X, Chen S, Wang J, Craigen WJ, Wong LJ.

Clin Genet. 2017 Apr;91(4):634-639. doi: 10.1111/cge.12894. Epub 2017 Jan 5.

PubMed [citation]
PMID:
27743463

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 Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV000598189.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The NM_012160.4:c.1687C>T (NP_036292.2:p.Gln563Ter) [GRCH38: NC_000006.12:g.98875430G>A] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:27743463 . This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PVS1:This variant is a predcted null variant in FBXL4 where loss of function is a known mechanism of disease. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 13 which is a recessive disorder. PP4:Patient’s phenotype or family history is highly specific for FBXL4. PP5:Reputable source(s) suggest that the variant is pathogenic. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Pathogenic.

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

Last Updated: Jun 23, 2024