rs121909299
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000436.4(OXCT1):c.848C>G(p.Ser283Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000695 in 1,439,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
OXCT1
NM_000436.4 stop_gained
NM_000436.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.49
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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;
PP5
?
Variant 5-41805674-G-C is Pathogenic according to our data. Variant chr5-41805674-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 8163.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OXCT1 | NM_000436.4 | c.848C>G | p.Ser283Ter | stop_gained | 9/17 | ENST00000196371.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OXCT1 | ENST00000196371.10 | c.848C>G | p.Ser283Ter | stop_gained | 9/17 | 1 | NM_000436.4 | P1 | |
OXCT1 | ENST00000509987.1 | c.290C>G | p.Ser97Ter | stop_gained | 5/13 | 2 | |||
OXCT1 | ENST00000514723.1 | n.144+34777C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251062Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135698
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GnomAD4 exome AF: 6.95e-7 AC: 1AN: 1439790Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 717694
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Succinyl-CoA acetoacetate transferase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1996 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at