NM_183050.4(BCKDHB):c.1159C>T (p.Arg387Ter) AND Maple syrup urine disease

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(2);Uncertain significance(1) (Last evaluated: Oct 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000671826.4

Allele description [Variation Report for NM_183050.4(BCKDHB):c.1159C>T (p.Arg387Ter)]

NM_183050.4(BCKDHB):c.1159C>T (p.Arg387Ter)

Gene:
BCKDHB:branched chain keto acid dehydrogenase E1 subunit beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q14.1
Genomic location:
Preferred name:
NM_183050.4(BCKDHB):c.1159C>T (p.Arg387Ter)
HGVS:
  • NC_000006.12:g.80343784C>T
  • NG_009775.1:g.242158C>T
  • NG_009775.2:g.242158C>T
  • NM_000056.4:c.1159C>T
  • NM_001318975.1:c.949C>T
  • NM_183050.4:c.1159C>TMANE SELECT
  • NP_000047.1:p.Arg387Ter
  • NP_001305904.1:p.Arg317Ter
  • NP_898871.1:p.Arg387Ter
  • NC_000006.11:g.81053501C>T
  • NM_183050.2:c.1159C>T
  • NR_134945.2:n.1276C>T
Protein change:
R317*
Links:
dbSNP: rs751599203
NCBI 1000 Genomes Browser:
rs751599203
Molecular consequence:
  • NR_134945.2:n.1276C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000056.4:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001318975.1:c.949C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_183050.4:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Maple syrup urine disease (MSUD)
Synonyms:
Branched chain ketoaciduria; Branched-chain alpha-keto acid dehydrogenase deficiency; Keto acid decarboxylase deficiency
Identifiers:
MONDO: MONDO:0009563; MeSH: D008375; MedGen: C0024776; Orphanet: 511; OMIM: 248600; OMIM: PS248600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000796849Counsylcriteria provided, single submitter
Uncertain significance
(Jan 5, 2018)
unknownclinical testing

Citation Link,

SCV000853150SingHealth Duke-NUS Institute of Precision Medicineno assertion criteria providedUncertain significance
(Jun 7, 2017)
germlinecuration

SCV001137189Mendelicscriteria provided, single submitter
Pathogenic
(May 28, 2019)
unknownclinical testing

Citation Link,

SCV001580943Invitaecriteria provided, single submitter
Pathogenic
(Oct 21, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedcuration
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population.

Ali EZ, Ngu LH.

Mol Genet Metab Rep. 2018 Dec;17:22-30. doi: 10.1016/j.ymgmr.2018.08.006.

PubMed [citation]
PMID:
30228974
PMCID:
PMC6140420

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Counsyl, SCV000796849.1

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

From SingHealth Duke-NUS Institute of Precision Medicine, SCV000853150.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Mendelics, SCV001137189.1

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

From Invitae, SCV001580943.1

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

Description

This sequence change results in a premature translational stop signal in the BCKDHB gene (p.Arg387*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acids of the BCKDHB protein. This variant is present in population databases (rs751599203, ExAC 0.02%). This variant has been observed in combination with another BCKDHB variant in several individuals affected with maple syrup urine disease (PMID: 30228974, Invitae). ClinVar contains an entry for this variant (Variation ID: 555909). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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