NM_000709.4(BCKDHA):c.1031C>T (p.Ala344Val) AND Maple syrup urine disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 3, 2020
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:: RCV003062657.2

Allele description [Variation Report for NM_000709.4(BCKDHA):c.1031C>T (p.Ala344Val)]

NM_000709.4(BCKDHA):c.1031C>T (p.Ala344Val)

Gene:

BCKDHA:branched chain keto acid dehydrogenase E1 subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_000709.4(BCKDHA):c.1031C>T (p.Ala344Val)

HGVS:

NC_000019.10:g.41423033C>T
NG_013004.1:g.30245C>T
NM_000709.4:c.1031C>TMANE SELECT
NM_001164783.2:c.1028C>T
NP_000700.1:p.Ala344Val
NP_001158255.1:p.Ala343Val
NC_000019.9:g.41928938C>T

Protein change:

A343V

Molecular consequence:

NM_000709.4:c.1031C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164783.2:c.1028C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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Homo sapiens THAP domain containing 3 (THAP3), transcript variant 2, mRNA
Homo sapiens THAP domain containing 3 (THAP3), transcript variant 2, mRNA
gi|2028695440|ref|NM_138350.4|

Nucleotide
Dmo1p [Saccharomyces cerevisiae S288C]
Dmo1p [Saccharomyces cerevisiae S288C]
gi|6322580|ref|NP_012654.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003449214	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 3, 2020)	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

SCV003449214

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 3, 2020)

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, SCV003449214.1

#	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 alanine with valine at codon 344 of the BCKDHA protein (p.Ala344Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs146300600, ExAC 0.009%). This variant has not been reported in the literature in individuals with BCKDHA-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: "Benign"; Align-GVGD: "Class C55"). 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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