Variant 1-54584688-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_147161.4(ACOT11):c.67C>T(p.Arg23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,614,172 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

ACOT11
NM_147161.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0620

Variant links:

Genes affected

ACOT11 (HGNC:18156): (acyl-CoA thioesterase 11) This gene encodes a member of the acyl-CoA thioesterase family which catalyse the conversion of activated fatty acids to the corresponding non-esterified fatty acid and coenzyme A. Expression of a mouse homolog in brown adipose tissue is induced by low temperatures and repressed by warm temperatures. Higher levels of expression of the mouse homolog has been found in obesity-resistant mice compared with obesity-prone mice, suggesting a role of acyl-CoA thioesterase 11 in obesity. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

ACOT11 links:

ACOT11 (HGNC:):

ACOT11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0124154985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOT11	NM_147161.4 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	2/16	ENST00000343744.7	NP_671517.1	Q8WXI4-2
ACOT11	NM_015547.4 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	2/17		NP_056362.1	Q8WXI4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACOT11	ENST00000343744.7 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	2/16	1	NM_147161.4	ENSP00000340260.2	Q8WXI4-2
ACOT11	ENST00000371316.3 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	2/17	1		ENSP00000360366.3	Q8WXI4-1
ACOT11	ENST00000481208.5 linkuse as main transcript	n.215C>T		non_coding_transcript_exon_variant	2/15	2
ACOT11	ENST00000498228.1 linkuse as main transcript	n.310C>T		non_coding_transcript_exon_variant	3/8	2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00251

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:

0.000112

AC:

AN:

250838

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00136

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000431

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000105

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000115

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.67C>T (p.R23W) alteration is located in exon 2 (coding exon 2) of the ACOT11 gene. This alteration results from a C to T substitution at nucleotide position 67, causing the arginine (R) at amino acid position 23 to be replaced by a tryptophan (W). 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

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.026

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.086

B;P

Vest4

0.29

MVP

0.30

MPC

0.75

ClinPred

0.092

GERP RS

2.9

Varity_R

0.085

gMVP

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over