NM_001278716.2(FBXL4):c.419T>C (p.Val140Ala) AND Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type)

Clinical significance:Likely pathogenic (Last evaluated: May 28, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000416414.4

Allele description [Variation Report for NM_001278716.2(FBXL4):c.419T>C (p.Val140Ala)]

NM_001278716.2(FBXL4):c.419T>C (p.Val140Ala)

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.419T>C (p.Val140Ala)
HGVS:
  • NC_000006.12:g.98926570A>G
  • NG_033903.1:g.26437T>C
  • NM_001278716.2:c.419T>CMANE SELECT
  • NM_012160.4:c.419T>C
  • NM_012160.5:c.419T>C
  • NP_001265645.1:p.Val140Ala
  • NP_036292.2:p.Val140Ala
  • NP_036292.2:p.Val140Ala
  • NC_000006.11:g.99374446A>G
  • NR_103836.2:n.750T>C
  • NR_103837.2:n.750T>C
Protein change:
V140A
Links:
dbSNP: rs1057519447
NCBI 1000 Genomes Browser:
rs1057519447
Molecular consequence:
  • NM_001278716.2:c.419T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012160.4:c.419T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012160.5:c.419T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_103836.2:n.750T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_103837.2:n.750T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) (MTDPS13)
Identifiers:
MONDO: MONDO:0014198; MedGen: C3809592; Orphanet: 369897; OMIM: 615471

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000494175Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicineno assertion criteria providedPathogenicgermlineresearch

SCV000598156Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicinecriteria provided, single submitter
Likely pathogenic
(Aug 10, 2017)
germlineclinical testing

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

SCV001137199Mendelicscriteria provided, single submitter
Likely pathogenic
(May 28, 2019)
unknownclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing, research
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine, SCV000494175.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided

Description

This variant was identified in an individual with developmental delay, hypotonia, muscle weakness, autistic features, lactic acidosis.

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

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV000598156.1

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

Description

The NM_012160.4:c.419T>C (NP_036292.2:p.Val140Ala) [GRCH38: NC_000006.12:g.98926570A>G] variant in FBXL4 gene is interpretated to be a Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG-guideline. 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. PP2:This is a missense variant in FBXL4 with a low rate of benign and high rate of pathogenic missense variations. PP3:Computational evidence/predictors indicate the variant has deleterious effect on FBXL4 structure, function, or protein-protein interaction. PP4:Patient’s phenotype or family history is highly specific for FBXL4. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Likely Pathogenic.

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

From Mendelics, SCV001137199.1

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

Last Updated: Oct 30, 2021

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