Genetic Variant OXCT1:c.-215A>G (chr5-41870573-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000972068.1(OXCT1):c.-215A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 594,638 control chromosomes in the GnomAD database, including 14,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3823 hom., cov: 33)

Exomes 𝑓: 0.22 ( 11156 hom. )

Consequence

OXCT1
ENST00000972068.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.384

Publications

9 publications found

Variant links:

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 links:

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

OXCT1-AS1 links:

LOC102723752 (HGNC:):

LOC102723752 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-41870573-T-C is Benign according to our data. Variant chr5-41870573-T-C is described in ClinVar as Benign. ClinVar VariationId is 353674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000972068.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OXCT1-AS1	NR_046635.1		n.255+191T>C	intron	N/A
OXCT1	NM_000436.4	MANE Select	c.-215A>G	upstream_gene	N/A	NP_000427.1	P55809-1
OXCT1	NM_001364299.2		c.-215A>G	upstream_gene	N/A	NP_001351228.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
OXCT1	ENST00000972068.1		c.-215A>G	5_prime_UTR	Exon 1 of 16	ENSP00000642127.1
OXCT1-AS1	ENST00000510509.1	TSL:3	n.356T>C	non_coding_transcript_exon	Exon 2 of 2
OXCT1-AS1	ENST00000654321.2		n.707T>C	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33522

AN:

152080

Hom.:

3808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.440

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.0325

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.236

GnomAD4 exome

AF:

0.217

AC:

95964

AN:

442440

Hom.:

11156

Cov.:

AF XY:

0.220

AC XY:

52050

AN XY:

236082

show subpopulations

African (AFR)

AF:

0.219

AC:

2712

AN:

12404

American (AMR)

AF:

0.258

AC:

5405

AN:

20948

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

3572

AN:

13722

East Asian (EAS)

AF:

0.0401

AC:

1187

AN:

29604

South Asian (SAS)

AF:

0.266

AC:

12644

AN:

47552

European-Finnish (FIN)

AF:

0.241

AC:

6545

AN:

27152

Middle Eastern (MID)

AF:

0.304

AC:

578

AN:

1904

European-Non Finnish (NFE)

AF:

0.218

AC:

57597

AN:

263964

Other (OTH)

AF:

0.227

AC:

5724

AN:

25190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

3522

7044

10565

14087

17609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

330

660

990

1320

1650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.221

AC:

33582

AN:

152198

Hom.:

3823

Cov.:

AF XY:

0.225

AC XY:

16734

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.215

AC:

8914

AN:

41526

American (AMR)

AF:

0.267

AC:

4087

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

869

AN:

3472

East Asian (EAS)

AF:

0.0325

AC:

168

AN:

5164

South Asian (SAS)

AF:

0.265

AC:

1279

AN:

4832

European-Finnish (FIN)

AF:

0.246

AC:

2609

AN:

10610

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14670

AN:

67988

Other (OTH)

AF:

0.236

AC:

497

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1354

2708

4063

5417

6771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.220

Hom.:

810

Bravo

AF:

0.218

Asia WGS

AF:

0.143

AC:

497

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Succinyl-CoA acetoacetate transferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.7

(source)

DANN

Benign

0.43

PhyloP100

-0.38

PromoterAI

0.42

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over