NM_000436.4:c.78+14dupG

Variant names:

• chr5-41870266-T-TC
• rs368390833
• NM_000436.4:c.78+14dupG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000436.4(OXCT1):​c.78+14dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,608,674 control chromosomes in the GnomAD database, including 853 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (100 hom., cov: 32)
  • Exomes 𝑓: 0.011 (753 hom.)
• Consequence: OXCT1 NM_000436.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: -0.667
• Publications: 0 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-AS1 (HGNC:40423): (OXCT1 antisense RNA 1)

LOC102723752 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 5-41870266-T-TC is Benign according to our data. Variant chr5-41870266-T-TC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000436.4. 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	NM_000436.4	MANE Select	c.78+14dupG		intron	N/A	NP_000427.1	P55809-1
	OXCT1	NM_001364300.2		c.-524dupG		5_prime_UTR	Exon 1 of 17	NP_001351229.1
	OXCT1	NM_001364299.2		c.78+14dupG		intron	N/A	NP_001351228.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXCT1	ENST00000196371.10	TSL:1 MANE Select	c.78+14dupG		intron	N/A	ENSP00000196371.5	P55809-1
	OXCT1	ENST00000972071.1		c.78+14dupG		intron	N/A	ENSP00000642130.1
	OXCT1	ENST00000919063.1		c.78+14dupG		intron	N/A	ENSP00000589122.1

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2140 AN: 152016 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.00280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0313 AC: 7843 AN: 250232 AF XY: 0.0296

Gnomad AFR exome AF: 0.00236

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0236

Gnomad FIN exome AF: 0.0205

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.0198

GnomAD4 exome AF: 0.0107 AC: 15539 AN: 1456540 Hom.: 753 Cov.: 29 AF XY: 0.0120 AC XY: 8729 AN XY: 725076

African (AFR) AF: 0.00165 AC: 55 AN: 33382

American (AMR) AF: 0.122 AC: 5462 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.000460 AC: 12 AN: 26088

East Asian (EAS) AF: 0.0368 AC: 1459 AN: 39672

South Asian (SAS) AF: 0.0716 AC: 6164 AN: 86102

European-Finnish (FIN) AF: 0.0205 AC: 1096 AN: 53404

Middle Eastern (MID) AF: 0.00625 AC: 36 AN: 5758

European-Non Finnish (NFE) AF: 0.000447 AC: 495 AN: 1107266

Other (OTH) AF: 0.0126 AC: 760 AN: 60180

GnomAD4 genome AF: 0.0142 AC: 2160 AN: 152134 Hom.: 100 Cov.: 32 AF XY: 0.0175 AC XY: 1298 AN XY: 74362

African (AFR) AF: 0.00279 AC: 116 AN: 41520

American (AMR) AF: 0.0759 AC: 1160 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.0314 AC: 161 AN: 5134

South Asian (SAS) AF: 0.0783 AC: 377 AN: 4816

European-Finnish (FIN) AF: 0.0224 AC: 238 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 67986

Other (OTH) AF: 0.0161 AC: 34 AN: 2108

Alfa AF: 0.00558 Hom.: 6

Bravo AF: 0.0168

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)
-	-	2	Succinyl-CoA acetoacetate transferase deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.67
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: rs368390833; hg19: chr5-41870368;