chr6-80106670-TGAGAATCCCGGTGGTGAGCGGGGATG-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_183050.4(BCKDHB):c.-22_4del variant causes a start lost, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
BCKDHB
NM_183050.4 start_lost, 5_prime_UTR
NM_183050.4 start_lost, 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.885
Genes affected
BCKDHB (HGNC:987): (branched chain keto acid dehydrogenase E1 subunit beta) This gene encodes the E1 beta subunit of branched-chain keto acid dehydrogenase, which is a multienzyme complex associated with the inner membrane of mitochondria. This enzyme complex functions in the catabolism of branched-chain amino acids. Mutations in this gene have been associated with maple syrup urine disease (MSUD), type 1B, a disease characterized by a maple syrup odor to the urine in addition to mental and physical retardation and feeding problems. Alternative splicing at this locus results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-80106670-TGAGAATCCCGGTGGTGAGCGGGGATG-T is Pathogenic according to our data. Variant chr6-80106670-TGAGAATCCCGGTGGTGAGCGGGGATG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 558247.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDHB | NM_183050.4 | c.-22_4del | start_lost, 5_prime_UTR_variant | 1/10 | ENST00000320393.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDHB | ENST00000320393.9 | c.-22_4del | start_lost, 5_prime_UTR_variant | 1/10 | 1 | NM_183050.4 | P1 | ||
BCKDHB | ENST00000356489.9 | c.-22_4del | start_lost, 5_prime_UTR_variant | 1/11 | 1 | P1 | |||
BCKDHB | ENST00000369760.8 | c.-22_4del | start_lost, 5_prime_UTR_variant | 1/6 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Maple syrup urine disease Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 08, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at