rs760851100
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_005881.4(BCKDK):c.847G>A(p.Ala283Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005881.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDK | NM_005881.4 | c.847G>A | p.Ala283Thr | missense_variant, splice_region_variant | 10/12 | ENST00000219794.11 | |
BCKDK | NM_001122957.4 | c.847G>A | p.Ala283Thr | missense_variant, splice_region_variant | 10/11 | ||
BCKDK | XM_017022859.2 | c.847G>A | p.Ala283Thr | missense_variant, splice_region_variant | 10/12 | ||
BCKDK | NM_001271926.3 | c.845+82G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDK | ENST00000219794.11 | c.847G>A | p.Ala283Thr | missense_variant, splice_region_variant | 10/12 | 1 | NM_005881.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251432Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135894
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14AN XY: 727236
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Branched-chain keto acid dehydrogenase kinase deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 25, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Mar 16, 2018 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2016 | The A283T variant in the BCKDK gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A283T variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A283T variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A283T as a variant of uncertain significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 27, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at