chr14-73619606-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365788.1(ACOT6):​c.1033C>T​(p.His345Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACOT6
NM_001365788.1 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
Variant links:
Genes affected
ACOT6 (HGNC:33159): (acyl-CoA thioesterase 6) Predicted to enable acyl-CoA hydrolase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACOT6NM_001365788.1 linkc.1033C>T p.His345Tyr missense_variant Exon 3 of 3 ENST00000645972.2 NP_001352717.1
ACOT6NM_001037162.1 linkc.391C>T p.His131Tyr missense_variant Exon 2 of 2 NP_001032239.1 Q3I5F7-2
ACOT6NM_001365789.1 linkc.391C>T p.His131Tyr missense_variant Exon 4 of 4 NP_001352718.1
HEATR4XM_047431370.1 linkc.-73+14055G>A intron_variant Intron 1 of 16 XP_047287326.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACOT6ENST00000645972.2 linkc.1033C>T p.His345Tyr missense_variant Exon 3 of 3 NM_001365788.1 ENSP00000496277.1 Q3I5F7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.391C>T (p.H131Y) alteration is located in exon 2 (coding exon 2) of the ACOT6 gene. This alteration results from a C to T substitution at nucleotide position 391, causing the histidine (H) at amino acid position 131 to be replaced by a tyrosine (Y). 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
0.092
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.048
.;.;T
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.21
FATHMM_MKL
Benign
0.59
D
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.56
D;D;D
MetaSVM
Benign
-0.91
T
MutationAssessor
Pathogenic
3.0
.;.;M
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-5.2
D;.;D
REVEL
Benign
0.17
Sift
Uncertain
0.024
D;.;D
Sift4G
Uncertain
0.034
D;.;D
Polyphen
0.82
.;.;P
Vest4
0.19
MutPred
0.77
Loss of disorder (P = 0.0516);.;Loss of disorder (P = 0.0516);
MVP
0.014
MPC
0.93
ClinPred
0.98
D
GERP RS
4.9
Varity_R
0.53
gMVP
0.54

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: chr14-74086310; API