NM_183050.4:c.152delT
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_183050.4(BCKDHB):c.152delT(p.Val51GlyfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_183050.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCKDHB | NM_183050.4 | c.152delT | p.Val51GlyfsTer21 | frameshift_variant | Exon 1 of 10 | ENST00000320393.9 | NP_898871.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BCKDHB | ENST00000320393.9 | c.152delT | p.Val51GlyfsTer21 | frameshift_variant | Exon 1 of 10 | 1 | NM_183050.4 | ENSP00000318351.5 | ||
BCKDHB | ENST00000356489.9 | c.152delT | p.Val51GlyfsTer21 | frameshift_variant | Exon 1 of 11 | 1 | ENSP00000348880.5 | |||
BCKDHB | ENST00000369760.8 | c.152delT | p.Val51GlyfsTer21 | frameshift_variant | Exon 1 of 6 | 3 | ENSP00000358775.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
Maple syrup urine disease Pathogenic:3
Variant summary: BCKDHB c.152delT (p.Val51GlyfsX21) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.2e-05 in 31374 control chromosomes (gnomAD). To our knowledge, no occurrence of c.152delT in individuals affected with Maple Syrup Urine Disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 527129). Based on the evidence outlined above, the variant was classified as pathogenic. -
For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Val51Glyfs*21) in the BCKDHB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BCKDHB are known to be pathogenic (PMID: 16786533, 22593002). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BCKDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 527129). -
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at