NM_183050.4(BCKDHB):c.403G>A (p.Gly135Arg) AND Maple syrup urine disease

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 6, 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:: RCV001796129.7

Allele description

NM_183050.4(BCKDHB):c.403G>A (p.Gly135Arg)

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.403G>A (p.Gly135Arg)

HGVS:

NC_000006.12:g.80167737G>A
NG_009775.2:g.66111G>A
NM_000056.5:c.403G>A
NM_001318975.1:c.193G>A
NM_183050.4:c.403G>AMANE SELECT
NP_000047.1:p.Gly135Arg
NP_001305904.1:p.Gly65Arg
NP_898871.1:p.Gly135Arg
NC_000006.11:g.80877454G>A
NM_183050.2:c.403G>A
NM_183050.3:c.403G>A
NR_134945.2:n.426G>A

Protein change:

G135R

Links:

dbSNP: rs751953459

NCBI 1000 Genomes Browser:

rs751953459

Molecular consequence:

NM_000056.5:c.403G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318975.1:c.193G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_183050.4:c.403G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134945.2:n.426G>A - 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
SCV002033144	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002807584	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 5, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003439997	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 6, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 14517957, 16786533, 24772966, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002033144

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 7, 2021)

germline

clinical testing

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

SCV002807584

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 5, 2022)

unknown

clinical testing

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

SCV003439997

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 6, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

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

Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease.

Henneke M, Flaschker N, Helbling C, Müller M, Schadewaldt P, Gärtner J, Wendel U.

Hum Mutat. 2003 Nov;22(5):417.

PubMed [citation]

PMID:: 14517957

See all PubMed Citations (5)

Details of each submission

From Genome-Nilou Lab, SCV002033144.1

#	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 Fulgent Genetics, Fulgent Genetics, SCV002807584.1

#	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

From Invitae, SCV003439997.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is present in population databases (rs751953459, gnomAD 0.0009%). ClinVar contains an entry for this variant (Variation ID: 496569). This missense change has been observed in individual(s) with maple syrup urine disease (PMID: 14517957, 16786533, 24772966). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 135 of the BCKDHB protein (p.Gly135Arg). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BCKDHB protein function.

#	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

Last Updated: Jun 23, 2024

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