1-39770205-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022120.2(OXCT2):āc.1051C>Gā(p.Pro351Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,422,548 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000017 ( 0 hom., cov: 16)
Exomes š: 0.0000023 ( 0 hom. )
Consequence
OXCT2
NM_022120.2 missense
NM_022120.2 missense
Scores
3
12
4
Clinical Significance
Conservation
PhyloP100: 2.71
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OXCT2 | NM_022120.2 | c.1051C>G | p.Pro351Ala | missense_variant | 1/1 | ENST00000327582.5 | NP_071403.1 | |
BMP8B | NM_001720.5 | c.673+4103C>G | intron_variant | ENST00000372827.8 | NP_001711.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OXCT2 | ENST00000327582.5 | c.1051C>G | p.Pro351Ala | missense_variant | 1/1 | 6 | NM_022120.2 | ENSP00000361914.1 | ||
BMP8B | ENST00000372827.8 | c.673+4103C>G | intron_variant | 1 | NM_001720.5 | ENSP00000361915.3 |
Frequencies
GnomAD3 genomes AF: 0.0000166 AC: 2AN: 120392Hom.: 0 Cov.: 16
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GnomAD4 exome AF: 0.00000230 AC: 3AN: 1302156Hom.: 0 Cov.: 28 AF XY: 0.00000156 AC XY: 1AN XY: 642990
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GnomAD4 genome AF: 0.0000166 AC: 2AN: 120392Hom.: 0 Cov.: 16 AF XY: 0.0000174 AC XY: 1AN XY: 57444
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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 | Dec 06, 2022 | The c.1051C>G (p.P351A) alteration is located in exon 1 (coding exon 1) of the OXCT2 gene. This alteration results from a C to G substitution at nucleotide position 1051, causing the proline (P) at amino acid position 351 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of loop (P = 0.069);
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