6-80106713-C-CT
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_183050.4(BCKDHB):c.21dupT(p.Ala8CysfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_183050.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCKDHB | NM_183050.4 | c.21dupT | p.Ala8CysfsTer13 | 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.21dupT | p.Ala8CysfsTer13 | frameshift_variant | Exon 1 of 10 | 1 | NM_183050.4 | ENSP00000318351.5 | ||
BCKDHB | ENST00000356489.9 | c.21dupT | p.Ala8CysfsTer13 | frameshift_variant | Exon 1 of 11 | 1 | ENSP00000348880.5 | |||
BCKDHB | ENST00000369760.8 | c.21dupT | p.Ala8CysfsTer13 | frameshift_variant | Exon 1 of 6 | 3 | ENSP00000358775.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 7.14e-7 AC: 1AN: 1399818Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1AN XY: 690904
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Maple syrup urine disease Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BCKDHB-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Ala8Cysfs*13) 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). -
Maple syrup urine disease type 1B Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.