5-41853412-T-G

Variant names:

Variant summary

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

The NM_000436.4(OXCT1):c.414+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 1,612,298 control chromosomes in the GnomAD database, including 6,945 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2560 hom., cov: 32)

Exomes 𝑓: 0.060 ( 4385 hom. )

Consequence

OXCT1
NM_000436.4 splice_region, intron

Scores

Splicing: ADA: 0.00006148

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.272

Publications

5 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 Gene-Disease associations (from GenCC):

succinyl-CoA:3-ketoacid CoA transferase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics, G2P, Illumina

OXCT1 links:

Genome browser will be placed here

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=-0.84).

BP6

Variant 5-41853412-T-G is Benign according to our data. Variant chr5-41853412-T-G is described in ClinVar as [Benign]. Clinvar id is 93004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXCT1	NM_000436.4 link	c.414+7A>C		splice_region_variant, intron_variant	Intron 4 of 16	ENST00000196371.10	NP_000427.1	P55809-1A0A024R040

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXCT1	ENST00000196371.10 link	c.414+7A>C		splice_region_variant, intron_variant	Intron 4 of 16	1	NM_000436.4	ENSP00000196371.5		P55809-1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19937

AN:

152028

Hom.:

2557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0718

Gnomad ASJ

AF:

0.0648

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0555

Gnomad FIN

AF:

0.0393

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0548

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.0685

AC:

17200

AN:

251012

AF XY:

0.0650

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.0421

Gnomad ASJ exome

AF:

0.0614

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0428

Gnomad NFE exome

AF:

0.0550

Gnomad OTH exome

AF:

0.0677

GnomAD4 exome

AF:

0.0601

AC:

87720

AN:

1460152

Hom.:

4385

Cov.:

AF XY:

0.0596

AC XY:

43324

AN XY:

726482

show subpopulations

African (AFR)

AF:

0.349

AC:

11668

AN:

33388

American (AMR)

AF:

0.0459

AC:

2051

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

1620

AN:

26112

East Asian (EAS)

AF:

0.000176

AC:

AN:

39676

South Asian (SAS)

AF:

0.0645

AC:

5556

AN:

86196

European-Finnish (FIN)

AF:

0.0400

AC:

2136

AN:

53334

Middle Eastern (MID)

AF:

0.0757

AC:

436

AN:

5762

European-Non Finnish (NFE)

AF:

0.0538

AC:

59726

AN:

1110660

Other (OTH)

AF:

0.0749

AC:

4520

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

3640

7281

10921

14562

18202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.131

AC:

19961

AN:

152146

Hom.:

2560

Cov.:

AF XY:

0.127

AC XY:

9463

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.336

AC:

13921

AN:

41460

American (AMR)

AF:

0.0717

AC:

1096

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0648

AC:

225

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.0547

AC:

264

AN:

4826

European-Finnish (FIN)

AF:

0.0393

AC:

417

AN:

10612

Middle Eastern (MID)

AF:

0.0719

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0548

AC:

3727

AN:

67992

Other (OTH)

AF:

0.120

AC:

254

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

773

1547

2320

3094

3867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0823

Hom.:

1592

Bravo

AF:

0.145

Asia WGS

AF:

0.0560

AC:

196

AN:

3478

EpiCase

AF:

0.0604

EpiControl

AF:

0.0583

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 20, 2021

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:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 06, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.9

(source)

DANN

Benign

0.50

PhyloP100

0.27

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000061

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

5-41853412-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over