5-41853412-T-G

Position:

• chr5-41853412-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000436.4(OXCT1):​c.414+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 1,612,298 control chromosomes in the GnomAD database, including 6,945 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2560 hom., cov: 32)
  • Exomes 𝑓: 0.060 (4385 hom.)
• Consequence: OXCT1 NM_000436.4 splice_region, intron
• Scores: Splicing: ADA: 0.00006148
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.272

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-41853412-T-G is Benign according to our data. Variant chr5-41853412-T-G is described in ClinVar as [Benign]. Clinvar id is 93004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXCT1	NM_000436.4	c.414+7A>C		splice_region_variant, intron_variant		ENST00000196371.10	NP_000427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXCT1	ENST00000196371.10	c.414+7A>C		splice_region_variant, intron_variant		1	NM_000436.4	ENSP00000196371.5

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19937 AN: 152028 Hom.: 2557 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.122

GnomAD3 exomes AF: 0.0685 AC: 17200 AN: 251012 Hom.: 1262 AF XY: 0.0650 AC XY: 8823 AN XY: 135690

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.0421

Gnomad ASJ exome AF: 0.0614

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0644

Gnomad FIN exome AF: 0.0428

Gnomad NFE exome AF: 0.0550

Gnomad OTH exome AF: 0.0677

GnomAD4 exome AF: 0.0601 AC: 87720 AN: 1460152 Hom.: 4385 Cov.: 31 AF XY: 0.0596 AC XY: 43324 AN XY: 726482

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.0459

Gnomad4 ASJ exome AF: 0.0620

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0645

Gnomad4 FIN exome AF: 0.0400

Gnomad4 NFE exome AF: 0.0538

Gnomad4 OTH exome AF: 0.0749

GnomAD4 genome AF: 0.131 AC: 19961 AN: 152146 Hom.: 2560 Cov.: 32 AF XY: 0.127 AC XY: 9463 AN XY: 74422

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.0717

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.0393

Gnomad4 NFE AF: 0.0548

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0740 Hom.: 1016

Bravo AF: 0.145

Asia WGS AF: 0.0560 AC: 196 AN: 3478

EpiCase AF: 0.0604

EpiControl AF: 0.0583

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Succinyl-CoA acetoacetate transferase deficiency Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 22, 2016	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 06, 2014	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000061
dbscSNV1_RF	Benign	0.0
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: rs7723992; hg19: chr5-41853514;