OXCT1 p.Ser283* – ACMG Classification: Pathogenic (10 pts)

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_000436.4(OXCT1):c.848C>A(p.Ser283*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OXCT1
NM_000436.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.49

Publications

0 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), Orphanet, Illumina, Ambry Genetics, G2P

OXCT1 links:

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new If you want to explore the variant's impact on the transcript NM_000436.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OXCT1	NM_000436.4	MANE Select	c.848C>A	p.Ser283*	stop_gained	Exon 9 of 17	NP_000427.1	P55809-1
OXCT1	NM_001364299.2		c.869C>A	p.Ser290*	stop_gained	Exon 10 of 18	NP_001351228.1
OXCT1	NM_001364300.2		c.869C>A	p.Ser290*	stop_gained	Exon 9 of 17	NP_001351229.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OXCT1	ENST00000196371.10	TSL:1 MANE Select	c.848C>A	p.Ser283*	stop_gained	Exon 9 of 17	ENSP00000196371.5	P55809-1
OXCT1	ENST00000972071.1		c.848C>A	p.Ser283*	stop_gained	Exon 9 of 18	ENSP00000642130.1
OXCT1	ENST00000919063.1		c.848C>A	p.Ser283*	stop_gained	Exon 9 of 18	ENSP00000589122.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1439790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717694

African (AFR)

AF:

0.00

AC:

AN:

33022

American (AMR)

AF:

0.00

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

39558

South Asian (SAS)

AF:

0.00

AC:

AN:

85798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092102

Other (OTH)

AF:

0.00

AC:

AN:

59670

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Uncertain

0.96

PhyloP100

5.5

Mutation Taster

=0/200

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over