chr16-31109536-TG-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_005881.4(BCKDK):c.222del(p.Met74IlefsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
BCKDK
NM_005881.4 frameshift
NM_005881.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.60
Genes affected
BCKDK (HGNC:16902): (branched chain keto acid dehydrogenase kinase) The branched-chain alpha-ketoacid dehydrogenase complex (BCKD) is an important regulator of the valine, leucine, and isoleucine catabolic pathways. The protein encoded by this gene is found in the mitochondrion, where it phosphorylates and inactivates BCKD. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 16-31109536-TG-T is Pathogenic according to our data. Variant chr16-31109536-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 39744.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDK | NM_005881.4 | c.222del | p.Met74IlefsTer15 | frameshift_variant | 3/12 | ENST00000219794.11 | |
BCKDK | NM_001122957.4 | c.222del | p.Met74IlefsTer15 | frameshift_variant | 3/11 | ||
BCKDK | NM_001271926.3 | c.222del | p.Met74IlefsTer15 | frameshift_variant | 3/10 | ||
BCKDK | XM_017022859.2 | c.222del | p.Met74IlefsTer15 | frameshift_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDK | ENST00000219794.11 | c.222del | p.Met74IlefsTer15 | frameshift_variant | 3/12 | 1 | NM_005881.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Branched-chain keto acid dehydrogenase kinase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 19, 2012 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at