rs774582968

Variant summary

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

The NM_006821.6(ACOT2):​c.554C>A​(p.Thr185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T185R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ACOT2
NM_006821.6 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.260
Variant links:
Genes affected
ACOT2 (HGNC:18431): (acyl-CoA thioesterase 2) This gene encodes a member of the acyl-CoA thioesterase protein family, and is one of four acyl-CoA hydrolase genes located in a cluster on chromosome 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13702035).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACOT2NM_006821.6 linkc.554C>A p.Thr185Lys missense_variant Exon 1 of 3 ENST00000238651.10 NP_006812.3 P49753-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACOT2ENST00000238651.10 linkc.554C>A p.Thr185Lys missense_variant Exon 1 of 3 1 NM_006821.6 ENSP00000238651.5 P49753-1
ACOT2ENST00000613168.1 linkc.494C>A p.Thr165Lys missense_variant Exon 1 of 3 1 ENSP00000477685.1 A0A087WT95
ACOT2ENST00000538782.2 linkn.96+398C>A intron_variant Intron 2 of 3 2 ENSP00000440961.2 F6VI00
ENSG00000258603ENST00000664243.1 linkn.63-11822G>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.03e-7
AC:
1
AN:
1422068
Hom.:
0
Cov.:
30
AF XY:
0.00000141
AC XY:
1
AN XY:
707842
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
Gnomad4 AMR exome
AF:
0.00
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
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
16
DANN
Benign
0.81
DEOGEN2
Benign
0.012
T;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.36
T;T;T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Uncertain
2.4
M;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.1
N;.;.
REVEL
Benign
0.11
Sift
Benign
0.099
T;.;.
Sift4G
Uncertain
0.035
D;D;D
Polyphen
0.0050
B;.;.
Vest4
0.16
MutPred
0.54
Gain of solvent accessibility (P = 0.0086);.;.;
MVP
0.71
ClinPred
0.11
T
GERP RS
1.4
Varity_R
0.095
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs774582968; hg19: chr14-74036498; API