rs775668624

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001386685.1(ACAT1):​c.-343C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ACAT1
NM_001386685.1 5_prime_UTR_premature_start_codon_gain

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.252
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22667307).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACAT1NM_000019.4 linkc.22C>A p.Leu8Met missense_variant Exon 1 of 12 ENST00000265838.9 NP_000010.1 P24752-1A0A140VJX1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACAT1ENST00000265838.9 linkc.22C>A p.Leu8Met missense_variant Exon 1 of 12 1 NM_000019.4 ENSP00000265838.4 P24752-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1398532
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
689976
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000279
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.061
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.49
T;T
M_CAP
Pathogenic
0.38
D
MetaRNN
Benign
0.23
T;T
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.010
N;N
REVEL
Benign
0.26
Sift
Benign
0.076
T;D
Sift4G
Benign
0.12
T;D
Polyphen
0.62
P;.
Vest4
0.29
MutPred
0.25
Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP
0.64
MPC
0.14
ClinPred
0.13
T
GERP RS
1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775668624; hg19: chr11-107992355; API