NM_183050.4(BCKDHB):c.1175A>G (p.Tyr392Cys) AND Maple syrup urine disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 4, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003072747.2

Allele description [Variation Report for NM_183050.4(BCKDHB):c.1175A>G (p.Tyr392Cys)]

NM_183050.4(BCKDHB):c.1175A>G (p.Tyr392Cys)

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.1175A>G (p.Tyr392Cys)

HGVS:

NC_000006.12:g.80343800A>G
NG_009775.3:g.242192A>G
NM_000056.5:c.1175A>G
NM_001318975.1:c.965A>G
NM_183050.2:c.1175A>G
NM_183050.4:c.1175A>GMANE SELECT
NP_000047.1:p.Tyr392Cys
NP_001305904.1:p.Tyr322Cys
NP_898871.1:p.Tyr392Cys
NC_000006.11:g.81053517A>G
NG_009775.2:g.242174A>G
NR_134945.2:n.1292A>G

Protein change:

Y322C

Molecular consequence:

NM_000056.5:c.1175A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001318975.1:c.965A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_183050.4:c.1175A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_134945.2:n.1292A>G - 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
SCV003471608	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 4, 2022)	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

SCV003471608

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 4, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003471608.1

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

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 392 of the BCKDHB protein (p.Tyr392Cys). This variant is present in population databases (rs547806898, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BCKDHB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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