rs774306610
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_183050.4(BCKDHB):c.564T>A(p.Cys188Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_183050.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDHB | NM_183050.4 | c.564T>A | p.Cys188Ter | stop_gained | 5/10 | ENST00000320393.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDHB | ENST00000320393.9 | c.564T>A | p.Cys188Ter | stop_gained | 5/10 | 1 | NM_183050.4 | P1 | |
BCKDHB | ENST00000356489.9 | c.564T>A | p.Cys188Ter | stop_gained | 5/11 | 1 | P1 | ||
BCKDHB | ENST00000369760.8 | c.564T>A | p.Cys188Ter | stop_gained | 5/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251402Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135876
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461854Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727236
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Maple syrup urine disease Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | This sequence change creates a premature translational stop signal (p.Cys188*) 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 present in population databases (rs774306610, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with maple syrup urine disease (PMID: 19480318). ClinVar contains an entry for this variant (Variation ID: 580585). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | National Newborn Screening Laboratory, Hospital Nacional de Niños | - | This is a null variant in a gene where the loss of function is a known disease mechanism, resulting in a truncated protein creating a premature stop codon. It is present in population databases in low frequency (gnomAD exomes: 0,00001; ExAC: 0,000008). This variant has been published in the literature associated with individuals with MSUD (PMID: 19480318). - |
Maple syrup urine disease type 1B Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 30, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at