5-41870306-C-A

Variant names:

• chr5-41870306-C-A
• rs867294018
• NM_000436.4:c.53G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000436.4(OXCT1):​c.53G>T​(p.Arg18Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OXCT1 NM_000436.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.819

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)

ENSG00000286164 (HGNC:):

ACMG classification

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=0.08985981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXCT1	NM_000436.4	c.53G>T	p.Arg18Leu	missense_variant	Exon 1 of 17	ENST00000196371.10	NP_000427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXCT1	ENST00000196371.10	c.53G>T	p.Arg18Leu	missense_variant	Exon 1 of 17	1	NM_000436.4	ENSP00000196371.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53G>T (p.R18L) alteration is located in exon 1 (coding exon 1) of the OXCT1 gene. This alteration results from a G to T substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a leucine (L). 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	Benign	0.13
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.74
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.24
Sift	Benign	0.79	T
Sift4G	Benign	0.25	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.50		Loss of methylation at R18 (P = 0.0016);
MVP		0.36
MPC		0.85
ClinPred		0.12	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.061
gMVP		0.74

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

Other links and lift over

dbSNP: rs867294018; hg19: chr5-41870408;