chr16-31109309-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005881.4(BCKDK):c.86C>T(p.Ala29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,607,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005881.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDK | NM_005881.4 | c.86C>T | p.Ala29Val | missense_variant | 2/12 | ENST00000219794.11 | |
BCKDK | NM_001122957.4 | c.86C>T | p.Ala29Val | missense_variant | 2/11 | ||
BCKDK | NM_001271926.3 | c.86C>T | p.Ala29Val | missense_variant | 2/10 | ||
BCKDK | XM_017022859.2 | c.86C>T | p.Ala29Val | missense_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDK | ENST00000219794.11 | c.86C>T | p.Ala29Val | missense_variant | 2/12 | 1 | NM_005881.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000126 AC: 3AN: 238220Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130538
GnomAD4 exome AF: 0.0000254 AC: 37AN: 1455546Hom.: 0 Cov.: 33 AF XY: 0.0000276 AC XY: 20AN XY: 723540
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74432
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2022 | The c.86C>T (p.A29V) alteration is located in exon 2 (coding exon 1) of the BCKDK gene. This alteration results from a C to T substitution at nucleotide position 86, causing the alanine (A) at amino acid position 29 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Branched-chain keto acid dehydrogenase kinase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces alanine with valine at codon 29 of the BCKDK protein (p.Ala29Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs762482788, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with BCKDK-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at