1-39770205-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022120.2(OXCT2):ā€‹c.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

Scores

3
12
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71
Variant links:
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
OXCT2NM_022120.2 linkuse as main transcriptc.1051C>G p.Pro351Ala missense_variant 1/1 ENST00000327582.5 NP_071403.1 Q9BYC2
BMP8BNM_001720.5 linkuse as main transcriptc.673+4103C>G intron_variant ENST00000372827.8 NP_001711.2 P34820-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OXCT2ENST00000327582.5 linkuse as main transcriptc.1051C>G p.Pro351Ala missense_variant 1/16 NM_022120.2 ENSP00000361914.1 Q9BYC2
BMP8BENST00000372827.8 linkuse as main transcriptc.673+4103C>G intron_variant 1 NM_001720.5 ENSP00000361915.3 P34820-1

Frequencies

GnomAD3 genomes
AF:
0.0000166
AC:
2
AN:
120392
Hom.:
0
Cov.:
16
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000333
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000230
AC:
3
AN:
1302156
Hom.:
0
Cov.:
28
AF XY:
0.00000156
AC XY:
1
AN XY:
642990
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000298
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000166
AC:
2
AN:
120392
Hom.:
0
Cov.:
16
AF XY:
0.0000174
AC XY:
1
AN XY:
57444
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000333
Gnomad4 OTH
AF:
0.00

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 submitterclinical testingAmbry GeneticsDec 06, 2022The 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.65
BayesDel_addAF
Uncertain
0.087
D
BayesDel_noAF
Benign
-0.11
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.68
D
Eigen
Benign
-0.071
Eigen_PC
Benign
-0.28
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Uncertain
0.28
D
MetaRNN
Uncertain
0.67
D
MetaSVM
Uncertain
0.29
D
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-7.8
D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
0.99
D
Vest4
0.36
MutPred
0.52
Gain of loop (P = 0.069);
MVP
0.79
ClinPred
1.0
D
GERP RS
1.5
Varity_R
0.67
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs934982130; hg19: chr1-40235877; API