16-31109395-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005881.4(BCKDK):c.172G>A(p.Ala58Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,455,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
BCKDK
NM_005881.4 missense
NM_005881.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 6.08
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.22354054).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDK | NM_005881.4 | c.172G>A | p.Ala58Thr | missense_variant | 2/12 | ENST00000219794.11 | |
BCKDK | NM_001122957.4 | c.172G>A | p.Ala58Thr | missense_variant | 2/11 | ||
BCKDK | NM_001271926.3 | c.172G>A | p.Ala58Thr | missense_variant | 2/10 | ||
BCKDK | XM_017022859.2 | c.172G>A | p.Ala58Thr | missense_variant | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDK | ENST00000219794.11 | c.172G>A | p.Ala58Thr | missense_variant | 2/12 | 1 | NM_005881.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1455604Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 2AN XY: 723184
GnomAD4 exome
AF:
AC:
3
AN:
1455604
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
723184
Gnomad4 AFR exome
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Gnomad4 ASJ exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2022 | The c.172G>A (p.A58T) alteration is located in exon 2 (coding exon 1) of the BCKDK gene. This alteration results from a G to A substitution at nucleotide position 172, causing the alanine (A) at amino acid position 58 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;D;D;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
B;.;.;B;.;.;.
Vest4
MutPred
Gain of phosphorylation at A58 (P = 0.0519);Gain of phosphorylation at A58 (P = 0.0519);Gain of phosphorylation at A58 (P = 0.0519);Gain of phosphorylation at A58 (P = 0.0519);Gain of phosphorylation at A58 (P = 0.0519);Gain of phosphorylation at A58 (P = 0.0519);Gain of phosphorylation at A58 (P = 0.0519);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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