chr6-80106694-A-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_001424043.1(BCKDHB):c.-164A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000965 in 1,554,802 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 Likely pathogenic (★★).
Frequency
Consequence
NM_001424043.1 5_prime_UTR_premature_start_codon_gain
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.1A>T | p.Met1? | initiator_codon_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.1A>T | p.Met1? | initiator_codon_variant | Exon 1 of 10 | 1 | NM_183050.4 | ENSP00000318351.5 | ||
BCKDHB | ENST00000356489.9 | c.1A>T | p.Met1? | initiator_codon_variant | Exon 1 of 11 | 1 | ENSP00000348880.5 | |||
BCKDHB | ENST00000369760.8 | c.1A>T | p.Met1? | initiator_codon_variant | Exon 1 of 6 | 3 | ENSP00000358775.4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152000Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000129 AC: 2AN: 155290Hom.: 0 AF XY: 0.0000120 AC XY: 1AN XY: 83284
GnomAD4 exome AF: 0.00000927 AC: 13AN: 1402802Hom.: 0 Cov.: 32 AF XY: 0.0000101 AC XY: 7AN XY: 692504
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152000Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74228
ClinVar
Submissions by phenotype
Maple syrup urine disease Pathogenic:2
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This sequence change affects the initiator methionine of the BCKDHB mRNA. The next in-frame methionine is located at codon 71. This variant is present in population databases (no rsID available, gnomAD 0.004%). Disruption of the initiator codon has been observed in individual(s) with maple syrup urine disease (PMID: 26257134, 31980395; Invitae). ClinVar contains an entry for this variant (Variation ID: 551456). For these reasons, this variant has been classified as Pathogenic. -
Maple syrup urine disease type 1B Pathogenic:2
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at