chr11-108121608-T-C
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1_SupportingPM2PP5_Very_Strong
The NM_000019.4(ACAT1):āc.2T>Cā(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 0.00000501 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 (ā ā ).
Frequency
Consequence
NM_000019.4 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACAT1 | NM_000019.4 | c.2T>C | p.Met1? | start_lost | Exon 1 of 12 | ENST00000265838.9 | NP_000010.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 0.00000501 AC: 7AN: 1398374Hom.: 0 Cov.: 37 AF XY: 0.00000580 AC XY: 4AN XY: 689860
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Deficiency of acetyl-CoA acetyltransferase Pathogenic:2
This sequence change affects the initiator methionine of the ACAT1 mRNA. The next in-frame methionine is located at codon 91. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 8103405, 12754704, 28220263). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 666461). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of the initiator codon affects ACAT1 function (PMID: 12754704). For these reasons, this variant has been classified as Pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at