VCV002798369.1 - ClinVar

NM_183050.4(BCKDHB):c.508_513del (p.Arg170_Ser171del)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_183050.4(BCKDHB):c.508_513del (p.Arg170_Ser171del)

Variation ID: 2798369 Accession: VCV002798369.1

Type and length

Deletion, 6 bp

Location

Cytogenetic: 6q14.1 6: 80168904-80168909 (GRCh38) [ NCBI UCSC ] 6: 80878621-80878626 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 20, 2024	Feb 20, 2024	Mar 17, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_183050.4:c.508_513del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_898871.1:p.Arg170_Ser171del	inframe deletion
NM_000056.5:c.508_513del	NP_000047.1:p.Arg170_Ser171del	inframe deletion
NM_001318975.1:c.298_303del	NP_001305904.1:p.Arg100_Ser101del	inframe deletion
NM_001424035.1:c.508_513del	NP_001410964.1:p.Arg170_Ser171del	inframe deletion
NM_001424036.1:c.508_513del	NP_001410965.1:p.Arg170_Ser171del	inframe deletion
NM_001424037.1:c.508_513del	NP_001410966.1:p.Arg170_Ser171del	inframe deletion
NM_001424038.1:c.508_513del	NP_001410967.1:p.Arg170_Ser171del	inframe deletion
NM_001424039.1:c.508_513del	NP_001410968.1:p.Arg170_Ser171del	inframe deletion
NM_001424040.1:c.508_513del	NP_001410969.1:p.Arg170_Ser171del	inframe deletion
NM_001424041.1:c.508_513del	NP_001410970.1:p.Arg170_Ser171del	inframe deletion
NM_001424042.1:c.508_513del	NP_001410971.1:p.Arg170_Ser171del	inframe deletion
NM_001424043.1:c.298_303del	NP_001410972.1:p.Arg100_Ser101del	inframe deletion
NM_001424044.1:c.508_513del	NP_001410973.1:p.Arg170_Ser171del	inframe deletion
NM_001424045.1:c.508_513del	NP_001410974.1:p.Arg170_Ser171del	inframe deletion
NR_134945.2:n.531_536del		non-coding transcript variant
NR_187561.1:n.531_536del		non-coding transcript variant
NR_187562.1:n.531_536del		non-coding transcript variant
NR_187563.1:n.531_536del		non-coding transcript variant
NR_187564.1:n.649_654del		non-coding transcript variant
NR_187565.1:n.531_536del		non-coding transcript variant
NC_000006.12:g.80168905_80168910del
NC_000006.11:g.80878622_80878627del
NG_009775.2:g.67279_67284del
NG_009775.3:g.67297_67302del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000006.12:80168903:TCGCTCT:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BCKDHB		-	-	GRCh38 GRCh37	780	800

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Maple syrup urine disease	Pathogenic (1)	criteria provided, single submitter	Mar 17, 2023	RCV003636366.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 17, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Maple syrup urine disease Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004394662.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024	Publications: PubMed (4) PubMed: 25381949‚ 26453840‚ 27682710‚ 29307017 Comment: For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BCKDHB protein in which other variant(s) (p.Arg170Cys) have … (more) For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BCKDHB protein in which other variant(s) (p.Arg170Cys) have been determined to be pathogenic (PMID: 25381949, 26453840, 27682710, 29307017). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with BCKDHB-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.508_513del, results in the deletion of 2 amino acid(s) of the BCKDHB protein (p.Arg170_Ser171del), but otherwise preserves the integrity of the reading frame. (less)

Comment:

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BCKDHB protein in which other variant(s) (p.Arg170Cys) have been determined to be pathogenic (PMID: 25381949, 26453840, 27682710, 29307017). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with BCKDHB-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.508_513del, results in the deletion of 2 amino acid(s) of the BCKDHB protein (p.Arg170_Ser171del), but otherwise preserves the integrity of the reading frame.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical characteristics and mutation analysis of five Chinese patients with maple syrup urine disease.	Li X	Metabolic brain disease	2018	PMID: 29307017
Co-existence of phenylketonuria either with maple syrup urine disease or Sandhoff disease in two patients from Iran: emphasizing the role of consanguinity.	Abiri M	Journal of pediatric endocrinology & metabolism : JPEM	2016	PMID: 27682710
Eleven novel mutations of the BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease in the Chinese population: Report on eight cases.	Li X	European journal of medical genetics	2015	PMID: 26453840
A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD).	Miryounesi M	Journal of pediatric endocrinology & metabolism : JPEM	2015	PMID: 25381949

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_183050.4(BCKDHB):c.508_513del (p.Arg170_Ser171del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...