rs11740946

Positions:

• chr5-41753701-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.1339-4094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,006 control chromosomes in the GnomAD database, including 4,432 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 0.24 (4432 hom., cov: 32)
• Consequence: OXCT1 NM_000436.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXCT1	NM_000436.4	c.1339-4094A>G		intron_variant		ENST00000196371.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXCT1	ENST00000196371.10	c.1339-4094A>G		intron_variant		1	NM_000436.4	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35792 AN: 151888 Hom.: 4419 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.236 AC: 35850 AN: 152006 Hom.: 4432 Cov.: 32 AF XY: 0.240 AC XY: 17794 AN XY: 74294

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0324

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.254

Alfa AF: 0.228 Hom.: 793

Bravo AF: 0.235

Asia WGS AF: 0.146 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	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

Other links and lift over

dbSNP: rs11740946; hg19: chr5-41753803;