chr11-108133847-AC-A
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000019.4(ACAT1):βc.149delβ(p.Thr50AsnfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 31)
Exomes π: 0.0000014 ( 0 hom. )
Consequence
ACAT1
NM_000019.4 frameshift
NM_000019.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.61
Genes affected
ACAT1 (HGNC:93): (acetyl-CoA acetyltransferase 1) This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA. Defects in this gene are associated with 3-ketothiolase deficiency, an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and butanone. [provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 11-108133847-AC-A is Pathogenic according to our data. Variant chr11-108133847-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 208341.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACAT1 | NM_000019.4 | c.149del | p.Thr50AsnfsTer7 | frameshift_variant | 3/12 | ENST00000265838.9 | NP_000010.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACAT1 | ENST00000265838.9 | c.149del | p.Thr50AsnfsTer7 | frameshift_variant | 3/12 | 1 | NM_000019.4 | ENSP00000265838 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251476Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135910
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727188
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deficiency of acetyl-CoA acetyltransferase Pathogenic:2
Pathogenic, criteria provided, single submitter | research | Department of Pediatrics, Gifu University | May 05, 2019 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1998 | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at