5-41870295-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000436.4(OXCT1):​c.64G>A​(p.Ala22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

OXCT1
NM_000436.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.388
Variant links:
Genes affected
OXCT1 (HGNC:8527): (3-oxoacid CoA-transferase 1) This gene encodes a member of the 3-oxoacid CoA-transferase gene family. The encoded protein is a homodimeric mitochondrial matrix enzyme that plays a central role in extrahepatic ketone body catabolism by catalyzing the reversible transfer of coenzyme A from succinyl-CoA to acetoacetate. Mutations in this gene are associated with succinyl CoA:3-oxoacid CoA transferase deficiency. [provided by RefSeq, Jul 2008]
OXCT1-AS1 (HGNC:40423): (OXCT1 antisense RNA 1)

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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=0.07829487).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OXCT1NM_000436.4 linkc.64G>A p.Ala22Thr missense_variant Exon 1 of 17 ENST00000196371.10 NP_000427.1 P55809-1A0A024R040

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OXCT1ENST00000196371.10 linkc.64G>A p.Ala22Thr missense_variant Exon 1 of 17 1 NM_000436.4 ENSP00000196371.5 P55809-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
9.4
DANN
Benign
0.67
DEOGEN2
Benign
0.075
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.25
T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.091
Sift
Benign
0.61
T
Sift4G
Benign
0.64
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.31
Loss of helix (P = 0.0237);
MVP
0.40
MPC
0.66
ClinPred
0.070
T
GERP RS
0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.064
gMVP
0.52

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: rs1750229851; hg19: chr5-41870397; API