rs10512793

Positions:

• chr5-41751600-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000436.4(OXCT1):​c.1339-1993A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,178 control chromosomes in the GnomAD database, including 1,127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1127 hom., cov: 32)
• Consequence: OXCT1 NM_000436.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXCT1	NM_000436.4	c.1339-1993A>G		intron_variant		ENST00000196371.10	NP_000427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXCT1	ENST00000196371.10	c.1339-1993A>G		intron_variant		1	NM_000436.4	ENSP00000196371	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17679 AN: 152060 Hom.: 1128 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17681 AN: 152178 Hom.: 1127 Cov.: 32 AF XY: 0.113 AC XY: 8420 AN XY: 74400

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0515

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.118

Alfa AF: 0.135 Hom.: 1866

Bravo AF: 0.116

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.77

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: rs10512793; hg19: chr5-41751702;