chr5-41870550-C-T

Variant names:

• chr5-41870550-C-T
• rs75587220
• ENST00000510509.1:n.333C>T

Variant summary

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

The ENST00000510509.1(OXCT1-AS1):​n.333C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 624,282 control chromosomes in the GnomAD database, including 670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (148 hom., cov: 33)
  • Exomes 𝑓: 0.042 (522 hom.)
• Consequence: OXCT1-AS1 ENST00000510509.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.395

Genes affected

OXCT1-AS1 (HGNC:40423): (OXCT1 antisense RNA 1)

ENSG00000286164 (HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 5-41870550-C-T is Benign according to our data. Variant chr5-41870550-C-T is described in ClinVar as [Benign]. Clinvar id is 353673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXCT1	NM_000436.4	c.-192G>A		upstream_gene_variant		ENST00000196371.10	NP_000427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXCT1	ENST00000196371.10	c.-192G>A		upstream_gene_variant		1	NM_000436.4	ENSP00000196371.5

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5460 AN: 152174 Hom.: 148 Cov.: 33

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0398

GnomAD4 exome AF: 0.0419 AC: 19771 AN: 471990 Hom.: 522 Cov.: 3 AF XY: 0.0403 AC XY: 10163 AN XY: 252236

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0246

Gnomad4 ASJ exome AF: 0.0372

Gnomad4 EAS exome AF: 0.0000325

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.0575

Gnomad4 NFE exome AF: 0.0527

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0359 AC: 5461 AN: 152292 Hom.: 148 Cov.: 33 AF XY: 0.0340 AC XY: 2536 AN XY: 74480

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0497

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0421 Hom.: 21

Bravo AF: 0.0338

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Succinyl-CoA acetoacetate transferase deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.64
CADD	Benign	11
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75587220; hg19: chr5-41870652;