5-41753701-T-C

Variant names:

• chr5-41753701-T-C
• rs11740946
• NM_000436.4:c.1339-4094A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• succinyl-CoA:3-ketoacid CoA transferase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics, G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OXCT1	NM_000436.4	c.1339-4094A>G		intron_variant	Intron 14 of 16	ENST00000196371.10	NP_000427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXCT1	ENST00000196371.10	c.1339-4094A>G		intron_variant	Intron 14 of 16	1	NM_000436.4	ENSP00000196371.5

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

African (AFR) AF: 0.269 AC: 11161 AN: 41470

American (AMR) AF: 0.275 AC: 4193 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 921 AN: 3472

East Asian (EAS) AF: 0.0324 AC: 167 AN: 5148

South Asian (SAS) AF: 0.267 AC: 1286 AN: 4816

European-Finnish (FIN) AF: 0.245 AC: 2595 AN: 10592

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14493 AN: 67946

Other (OTH) AF: 0.254 AC: 535 AN: 2108

Alfa AF: 0.228 Hom.: 816

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
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11740946; hg19: chr5-41753803;