NM_183050.4(BCKDHB):c.368del (p.Pro123fs) AND Maple syrup urine disease

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Nov 7, 2021
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:: RCV000490444.8

Allele description [Variation Report for NM_183050.4(BCKDHB):c.368del (p.Pro123fs)]

NM_183050.4(BCKDHB):c.368del (p.Pro123fs)

Gene:

BCKDHB:branched chain keto acid dehydrogenase E1 subunit beta [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6q14.1

Genomic location:

Preferred name:

NM_183050.4(BCKDHB):c.368del (p.Pro123fs)

HGVS:

NC_000006.12:g.80167702del
NG_009775.2:g.66076del
NM_000056.5:c.368del
NM_001318975.1:c.158del
NM_183050.4:c.368delMANE SELECT
NP_000047.1:p.Pro123fs
NP_001305904.1:p.Pro53fs
NP_898871.1:p.Pro123fs
NC_000006.11:g.80877416del
NC_000006.11:g.80877419del
NM_000056.3:c.368delC
NR_134945.2:n.391del

Protein change:

P123fs

Links:

dbSNP: rs1085307058

NCBI 1000 Genomes Browser:

rs1085307058

Molecular consequence:

NM_000056.5:c.368del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318975.1:c.158del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_183050.4:c.368del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_134945.2:n.391del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000267225	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 18, 2016)	germline	reference population	PubMed (2) [See all records that cite these PMIDs] 14742428, 25741868
SCV001585234	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 17, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16786533, 22593002, 28492532
SCV002033143	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]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000267225

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 18, 2016)

germline

reference population

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

SCV001585234

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 17, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002033143

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]

Help

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
East Asian	germline	unknown	1	not provided	not provided	not provided	not provided	reference population

Citations

PubMed

Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype.

Chuang JL, Wynn RM, Moss CC, Song JL, Li J, Awad N, Mandel H, Chuang DT.

J Biol Chem. 2004 Apr 23;279(17):17792-800. Epub 2004 Jan 23.

PubMed [citation]

PMID:: 14742428

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 Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center, SCV000267225.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	East Asian	1	not provided	not provided	reference population	PubMed (2)

#	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		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001585234.4

#	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. Loss-of-function variants in BCKDHB are known to be pathogenic (PMID: 16786533, 22593002). This variant has not been reported in the literature in individuals with BCKDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 225303). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro123Hisfs*107) in the BCKDHB gene. It is expected to result in an absent or disrupted protein product.

#	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 Genome-Nilou Lab, SCV002033143.1

#	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

Last Updated: Sep 29, 2024

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