rs120074142
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_SupportingPM2PP5_Moderate
The NM_000019.4(ACAT1):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,374 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 (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000029 ( 0 hom. )
Consequence
ACAT1
NM_000019.4 start_lost
NM_000019.4 start_lost
Scores
6
4
6
Clinical Significance
Conservation
PhyloP100: 1.55
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 Uncertain_significance. Variant got 5 ACMG points.
PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 270 CDS bases. Genomic position: 108134252. Lost 0.210 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-108121608-T-A is Pathogenic according to our data. Variant chr11-108121608-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 2838.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACAT1 | NM_000019.4 | c.2T>A | p.Met1? | start_lost | Exon 1 of 12 | ENST00000265838.9 | NP_000010.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD4 exome AF: 0.00000286 AC: 4AN: 1398374Hom.: 0 Cov.: 37 AF XY: 0.00000290 AC XY: 2AN XY: 689860
GnomAD4 exome
AF:
AC:
4
AN:
1398374
Hom.:
Cov.:
37
AF XY:
AC XY:
2
AN XY:
689860
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deficiency of acetyl-CoA acetyltransferase Pathogenic:2
Jan 01, 1993
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
May 05, 2019
Department of Pediatrics, Gifu University
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
B;.
Vest4
MutPred
Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at