chr16-31109564-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005881.4(BCKDK):c.249C>A(p.Asp83Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D83D) has been classified as Benign.
Frequency
Consequence
NM_005881.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDK | NM_005881.4 | c.249C>A | p.Asp83Glu | missense_variant | 3/12 | ENST00000219794.11 | |
BCKDK | NM_001122957.4 | c.249C>A | p.Asp83Glu | missense_variant | 3/11 | ||
BCKDK | NM_001271926.3 | c.249C>A | p.Asp83Glu | missense_variant | 3/10 | ||
BCKDK | XM_017022859.2 | c.249C>A | p.Asp83Glu | missense_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDK | ENST00000219794.11 | c.249C>A | p.Asp83Glu | missense_variant | 3/12 | 1 | NM_005881.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461808Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727204
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2017 | The D83E variant in the BCKDK gene has not been reported previously as a pathogenic variant, noras a benign variant, to our knowledge. The D83E variant was not observed in approximately 6500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The D83E variant is a conservativeamino acid substitution, which is not likely to impact secondary protein structure as these residuesshare similar properties. However, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Weinterpret D83E as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at