14-73619663-C-T

Variant summary

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

The NM_001365788.1(ACOT6):​c.1090C>T​(p.Pro364Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ACOT6
NM_001365788.1 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55
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.1090C>T p.Pro364Ser missense_variant Exon 3 of 3 ENST00000645972.2 NP_001352717.1
ACOT6NM_001037162.1 linkc.448C>T p.Pro150Ser missense_variant Exon 2 of 2 NP_001032239.1 Q3I5F7-2
ACOT6NM_001365789.1 linkc.448C>T p.Pro150Ser missense_variant Exon 4 of 4 NP_001352718.1
HEATR4XM_047431370.1 linkc.-73+13998G>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.1090C>T p.Pro364Ser missense_variant Exon 3 of 3 NM_001365788.1 ENSP00000496277.1 Q3I5F7-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251408
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461852
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.448C>T (p.P150S) 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 448, causing the proline (P) at amino acid position 150 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.099
.;.;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.97
D;D;D
M_CAP
Benign
0.059
D
MetaRNN
Uncertain
0.63
D;D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Pathogenic
3.4
.;.;M
PrimateAI
Benign
0.45
T
PROVEAN
Pathogenic
-7.8
D;.;D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0040
D;.;D
Sift4G
Pathogenic
0.0
D;.;D
Polyphen
1.0
.;.;D
Vest4
0.48
MVP
0.19
MPC
0.90
ClinPred
0.97
D
GERP RS
4.7
Varity_R
0.80
gMVP
0.68

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: rs576704472; hg19: chr14-74086367; API