6-159762928-A-G

Variant summary

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

The NM_005891.3(ACAT2):ā€‹c.65A>Gā€‹(p.Asn22Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,612,304 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N22T) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.00028 ( 0 hom., cov: 32)
Exomes š‘“: 0.000082 ( 1 hom. )

Consequence

ACAT2
NM_005891.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09456614).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACAT2NM_005891.3 linkuse as main transcriptc.65A>G p.Asn22Ser missense_variant 2/9 ENST00000367048.5
ACAT2NM_001303253.1 linkuse as main transcriptc.152A>G p.Asn51Ser missense_variant 2/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACAT2ENST00000367048.5 linkuse as main transcriptc.65A>G p.Asn22Ser missense_variant 2/91 NM_005891.3 P1Q9BWD1-1
ACAT2ENST00000467951.1 linkuse as main transcriptn.293A>G non_coding_transcript_exon_variant 2/53

Frequencies

GnomAD3 genomes
AF:
0.000276
AC:
42
AN:
152140
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00242
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000132
AC:
33
AN:
249328
Hom.:
0
AF XY:
0.000126
AC XY:
17
AN XY:
134860
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000498
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.000232
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000822
AC:
120
AN:
1460046
Hom.:
1
Cov.:
32
AF XY:
0.0000909
AC XY:
66
AN XY:
726392
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000406
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000929
Gnomad4 FIN exome
AF:
0.000262
Gnomad4 NFE exome
AF:
0.0000630
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000276
AC:
42
AN:
152258
Hom.:
0
Cov.:
32
AF XY:
0.000363
AC XY:
27
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00242
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.000159
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 GeneticsDec 20, 2023The c.65A>G (p.N22S) alteration is located in exon 2 (coding exon 2) of the ACAT2 gene. This alteration results from a A to G substitution at nucleotide position 65, causing the asparagine (N) at amino acid position 22 to be replaced by a serine (S). 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
0.083
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
21
DANN
Benign
0.89
DEOGEN2
Uncertain
0.59
D
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.39
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.095
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.16
Sift
Benign
0.17
T
Sift4G
Benign
0.12
T
Polyphen
0.023
B
Vest4
0.35
MVP
0.40
MPC
0.10
ClinPred
0.074
T
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.48
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs199953042; hg19: chr6-160183960; COSMIC: COSV65455168; COSMIC: COSV65455168; API