chr5-41870704-C-T

Variant names:

• chr5-41870704-C-T
• rs138037654
• ENST00000510509.1:n.487C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000510509.1(OXCT1-AS1):​n.487C>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 0.00526 in 384,418 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0099 (26 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (2 hom.)
• Consequence: OXCT1-AS1 ENST00000510509.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33
• Publications: 2 publications found

Genes affected

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

LOC102723752 (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]

OXCT1 Gene-Disease associations (from GenCC):

• succinyl-CoA:3-ketoacid CoA transferase deficiency

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-41870704-C-T is Benign according to our data. Variant chr5-41870704-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 369475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0099 (1507/152296) while in subpopulation AFR AF = 0.0306 (1271/41564). AF 95% confidence interval is 0.0292. There are 26 homozygotes in GnomAd4. There are 711 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510509.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXCT1-AS1	NR_046635.1		n.256-62C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXCT1-AS1	ENST00000510509.1	TSL:3	n.487C>T		non_coding_transcript_exon	Exon 2 of 2
	OXCT1-AS1	ENST00000654321.2		n.838C>T		non_coding_transcript_exon	Exon 2 of 2
	OXCT1-AS1	ENST00000791754.1		n.90C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00986 AC: 1501 AN: 152180 Hom.: 25 Cov.: 33

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00957

GnomAD4 exome AF: 0.00222 AC: 516 AN: 232122 Hom.: 2 Cov.: 0 AF XY: 0.00209 AC XY: 264 AN XY: 126222

African (AFR) AF: 0.0323 AC: 208 AN: 6436

American (AMR) AF: 0.00495 AC: 59 AN: 11920

Ashkenazi Jewish (ASJ) AF: 0.00584 AC: 35 AN: 5992

East Asian (EAS) AF: 0.00 AC: 0 AN: 10730

South Asian (SAS) AF: 0.000401 AC: 17 AN: 42430

European-Finnish (FIN) AF: 0.000774 AC: 8 AN: 10330

Middle Eastern (MID) AF: 0.00463 AC: 4 AN: 864

European-Non Finnish (NFE) AF: 0.00106 AC: 140 AN: 131498

Other (OTH) AF: 0.00377 AC: 45 AN: 11922

GnomAD4 genome AF: 0.00990 AC: 1507 AN: 152296 Hom.: 26 Cov.: 33 AF XY: 0.00955 AC XY: 711 AN XY: 74472

African (AFR) AF: 0.0306 AC: 1271 AN: 41564

American (AMR) AF: 0.00483 AC: 74 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 68018

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00595 Hom.: 0

Bravo AF: 0.0110

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Succinyl-CoA acetoacetate transferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.50
DANN	Benign	0.77
PhyloP100		-1.3
PromoterAI		-0.028	Neutral

Splicing

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

Other links and lift over

dbSNP: rs138037654; hg19: chr5-41870806;