NM_183050.4(BCKDHB):c.487G>T (p.Glu163Ter) AND Maple syrup urine disease

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Apr 4, 2023
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:: RCV000409047.11

Allele description [Variation Report for NM_183050.4(BCKDHB):c.487G>T (p.Glu163Ter)]

NM_183050.4(BCKDHB):c.487G>T (p.Glu163Ter)

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.487G>T (p.Glu163Ter)

HGVS:

NC_000006.12:g.80168884G>T
NG_009775.2:g.67258G>T
NM_000056.5:c.487G>T
NM_001318975.1:c.277G>T
NM_183050.4:c.487G>TMANE SELECT
NP_000047.1:p.Glu163Ter
NP_001305904.1:p.Glu93Ter
NP_898871.1:p.Glu163Ter
NC_000006.11:g.80878601G>T
NM_183050.2:c.487G>T
NM_183050.3:c.487G>T
NR_134945.2:n.510G>T

Protein change:

E163*

Links:

dbSNP: rs1057516799

NCBI 1000 Genomes Browser:

rs1057516799

Molecular consequence:

NR_134945.2:n.510G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000056.5:c.487G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001318975.1:c.277G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_183050.4:c.487G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Maple syrup urine disease (MSUD)
Identifiers:: MONDO: MONDO:0009563; MeSH: D008375; MedGen: C0024776; Orphanet: 511; OMIM: PS248600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000486238	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Pathogenic (Apr 22, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16786533, 8430702 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV002033146	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002238420	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16786533, 22593002, 28492532
SCV004215990	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 4, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple-exon skipping as a secondary effect of the mutations.

Fisher CW, Fisher CR, Chuang JL, Lau KS, Chuang DT, Cox RP.

Am J Hum Genet. 1993 Feb;52(2):414-24.

PubMed [citation]

PMID:: 8430702
PMCID:: PMC1682180

Mutational spectrum of maple syrup urine disease in Spain.

Rodríguez-Pombo P, Navarrete R, Merinero B, Gómez-Puertas P, Ugarte M.

Hum Mutat. 2006 Jul;27(7):715.

PubMed [citation]

PMID:: 16786533

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000486238.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002033146.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002238420.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370827). This premature translational stop signal has been observed in individual(s) with maple syrup urine disease (PMID: 16786533). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu163*) in the BCKDHB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BCKDHB are known to be pathogenic (PMID: 16786533, 22593002).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004215990.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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