1-39770423-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022120.2(OXCT2):c.833G>T(p.Arg278Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,608,638 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 (★).
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 22)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
OXCT2
NM_022120.2 missense
NM_022120.2 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 0.849
Genes affected
OXCT2 (HGNC:18606): (3-oxoacid CoA-transferase 2) The protein encoded by this gene catalyzes the transfer of a CoA group from succinate to acetoacetate and is an important enzyme in ketone body catabolism. The encoded protein localizes to the mitochondrion. This gene is intronless, and a pseudogene of this gene is located elsewhere on chromosome 1. [provided by RefSeq, Aug 2016]
BMP8B (HGNC:1075): (bone morphogenetic protein 8b) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The encoded protein stimulates thermogenesis in brown adipose tissue. Expression of this gene may be downregulated in pancreatic cancer. This gene may have arose from a gene duplication event and its gene duplicate is also present on chromosome 1. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29833114).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OXCT2 | NM_022120.2 | c.833G>T | p.Arg278Leu | missense_variant | 1/1 | ENST00000327582.5 | NP_071403.1 | |
BMP8B | NM_001720.5 | c.673+3885G>T | intron_variant | ENST00000372827.8 | NP_001711.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OXCT2 | ENST00000327582.5 | c.833G>T | p.Arg278Leu | missense_variant | 1/1 | 6 | NM_022120.2 | ENSP00000361914.1 | ||
BMP8B | ENST00000372827.8 | c.673+3885G>T | intron_variant | 1 | NM_001720.5 | ENSP00000361915.3 |
Frequencies
GnomAD3 genomes AF: 0.00000673 AC: 1AN: 148694Hom.: 0 Cov.: 22
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459828Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726224
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GnomAD4 genome AF: 0.00000672 AC: 1AN: 148810Hom.: 0 Cov.: 22 AF XY: 0.0000137 AC XY: 1AN XY: 72770
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 10, 2023 | The c.833G>T (p.R278L) alteration is located in exon 1 (coding exon 1) of the OXCT2 gene. This alteration results from a G to T substitution at nucleotide position 833, causing the arginine (R) at amino acid position 278 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0094);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at