5-41730295-C-G

Position:

• chr5-41730295-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000436.4(OXCT1):​c.*1434G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 152,264 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (99 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OXCT1 NM_000436.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.673

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-41730295-C-G is Benign according to our data. Variant chr5-41730295-C-G is described in ClinVar as [Benign]. Clinvar id is 353645.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXCT1	NM_000436.4	c.*1434G>C		3_prime_UTR_variant	17/17	ENST00000196371.10	NP_000427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXCT1	ENST00000196371.10	c.*1434G>C		3_prime_UTR_variant	17/17	1	NM_000436.4	ENSP00000196371	P1

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2152 AN: 152146 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0139

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 EAS exome AF: 0.00

GnomAD4 genome AF: 0.0143 AC: 2172 AN: 152264 Hom.: 99 Cov.: 32 AF XY: 0.0176 AC XY: 1307 AN XY: 74450

Gnomad4 AFR AF: 0.00274

Gnomad4 AMR AF: 0.0756

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0338

Gnomad4 SAS AF: 0.0794

Gnomad4 FIN AF: 0.0220

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00720 Hom.: 5

Bravo AF: 0.0169

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Succinyl-CoA acetoacetate transferase deficiency Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.56
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs77675837; hg19: chr5-41730397;