6-159767007-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005891.3(ACAT2):ā€‹c.193T>Gā€‹(p.Cys65Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ACAT2
NM_005891.3 missense, splice_region

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78
Variant links:
Genes affected
ACAT2 (HGNC:94): (acetyl-CoA acetyltransferase 2) The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase. This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34393263).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACAT2NM_005891.3 linkuse as main transcriptc.193T>G p.Cys65Gly missense_variant, splice_region_variant 3/9 ENST00000367048.5
ACAT2NM_001303253.1 linkuse as main transcriptc.280T>G p.Cys94Gly missense_variant, splice_region_variant 3/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACAT2ENST00000367048.5 linkuse as main transcriptc.193T>G p.Cys65Gly missense_variant, splice_region_variant 3/91 NM_005891.3 P1Q9BWD1-1
ACAT2ENST00000467951.1 linkuse as main transcriptn.421T>G splice_region_variant, non_coding_transcript_exon_variant 3/53

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461678
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
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

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 18, 2023The c.193T>G (p.C65G) alteration is located in exon 3 (coding exon 3) of the ACAT2 gene. This alteration results from a T to G substitution at nucleotide position 193, causing the cysteine (C) at amino acid position 65 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
22
DANN
Benign
0.87
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.0081
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.074
D
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-0.52
T
MutationAssessor
Benign
0.095
N
MutationTaster
Benign
0.92
D;D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.13
N
REVEL
Uncertain
0.37
Sift
Benign
0.27
T
Sift4G
Benign
0.38
T
Polyphen
0.070
B
Vest4
0.44
MVP
0.94
MPC
0.24
ClinPred
0.30
T
GERP RS
5.7
Varity_R
0.34
gMVP
0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-160188039; API