1-39769997-A-G

Variant summary

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

The NM_022120.2(OXCT2):ā€‹c.1259T>Cā€‹(p.Met420Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,367,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000072 ( 0 hom., cov: 19)
Exomes š‘“: 0.0000044 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OXCT2
NM_022120.2 missense

Scores

4
12
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48
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]

Genome browser will be placed here

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 UniProt
OXCT2NM_022120.2 linkuse as main transcriptc.1259T>C p.Met420Thr missense_variant 1/1 ENST00000327582.5
BMP8BNM_001720.5 linkuse as main transcriptc.673+4311T>C intron_variant ENST00000372827.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OXCT2ENST00000327582.5 linkuse as main transcriptc.1259T>C p.Met420Thr missense_variant 1/1 NM_022120.2 P1
BMP8BENST00000372827.8 linkuse as main transcriptc.673+4311T>C intron_variant 1 NM_001720.5 P1P34820-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
139466
Hom.:
0
Cov.:
19
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000705
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000439
AC:
6
AN:
1367836
Hom.:
0
Cov.:
31
AF XY:
0.00000148
AC XY:
1
AN XY:
673812
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:
0.00000378
Gnomad4 OTH exome
AF:
0.0000176
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000717
AC:
1
AN:
139466
Hom.:
0
Cov.:
19
AF XY:
0.00
AC XY:
0
AN XY:
67294
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000705
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
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 GeneticsOct 26, 2022The c.1259T>C (p.M420T) alteration is located in exon 1 (coding exon 1) of the OXCT2 gene. This alteration results from a T to C substitution at nucleotide position 1259, causing the methionine (M) at amino acid position 420 to be replaced by a threonine (T). 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
0.88
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.74
D
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.037
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.80
T
M_CAP
Uncertain
0.093
D
MetaRNN
Uncertain
0.66
D
MetaSVM
Uncertain
0.48
D
MutationAssessor
Pathogenic
4.3
H
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Pathogenic
0.71
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.0060
D
Polyphen
1.0
D
Vest4
0.38
MutPred
0.78
Loss of sheet (P = 0.0315);
MVP
1.0
ClinPred
1.0
D
GERP RS
2.4
Varity_R
0.65
gMVP
0.69

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: rs1363645953; hg19: chr1-40235669; API