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NM_001278716.2(FBXL4):c.316C>T (p.Gln106Ter) AND Mitochondrial DNA depletion syndrome 13

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 16, 2017
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:
RCV000503270.7

Allele description [Variation Report for NM_001278716.2(FBXL4):c.316C>T (p.Gln106Ter)]

NM_001278716.2(FBXL4):c.316C>T (p.Gln106Ter)

Gene:
FBXL4:F-box and leucine rich repeat protein 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q16.2
Genomic location:
Preferred name:
NM_001278716.2(FBXL4):c.316C>T (p.Gln106Ter)
HGVS:
  • NC_000006.12:g.98926673G>A
  • NG_033903.1:g.26334C>T
  • NM_001278716.2:c.316C>TMANE SELECT
  • NM_012160.5:c.316C>T
  • NP_001265645.1:p.Gln106Ter
  • NP_036292.2:p.Gln106Ter
  • NP_036292.2:p.Gln106Ter
  • NC_000006.11:g.99374549G>A
  • NM_012160.4:c.316C>T
  • NR_103836.2:n.647C>T
  • NR_103837.2:n.647C>T
Protein change:
Q106*
Links:
dbSNP: rs1554222122
NCBI 1000 Genomes Browser:
rs1554222122
Molecular consequence:
  • NR_103836.2:n.647C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_103837.2:n.647C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001278716.2:c.316C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012160.5:c.316C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

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
SCV000598184Wong 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]

SCV000680234Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
criteria provided, single submitter

(Classification criteria August 2017)		Pathogenic
(Nov 16, 2017) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing

Citations

PubMed

Clinical, morphological, biochemical, imaging and outcome parameters in 21 individuals with mitochondrial maintenance defect related to FBXL4 mutations.

Huemer M, Karall D, Schossig A, Abdenur JE, Al Jasmi F, Biagosch C, Distelmaier F, Freisinger P, Graham BH, Haack TB, Hauser N, Hertecant J, Ebrahimi-Fakhari D, Konstantopoulou V, Leydiker K, Lourenco CM, Scholl-Bürgi S, Wilichowski E, Wolf NI, Wortmann SB, Taylor RW, Mayr JA, et al.

J Inherit Metab Dis. 2015 Sep;38(5):905-14. doi: 10.1007/s10545-015-9836-6. Epub 2015 Apr 14.

PubMed [citation]
PMID:
25868664
PMCID:
PMC4841446

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, SCV000598184.1

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

Description

The NM_012160.4:c.316C>T (NP_036292.2:p.Gln106Ter) [GRCH38: NC_000006.12:g.98926673G>A] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:25868664 . 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

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV000680234.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1bloodnot provided1not providednot providednot provided

Last Updated: Jun 23, 2024