chr1-54548341-G-A

Position:

chr1-54548341-G-A

Variant summary

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

The NM_147161.4(ACOT11):c.32G>A(p.Arg11Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000425 in 1,601,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

ACOT11
NM_147161.4 missense, splice_region

Scores

Splicing: ADA: 0.0007717

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.835

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 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=0.1327649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOT11	NM_147161.4 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant, splice_region_variant	1/16	ENST00000343744.7	NP_671517.1	Q8WXI4-2
ACOT11	NM_015547.4 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant, splice_region_variant	1/17		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.32G>A	p.Arg11Gln	missense_variant, splice_region_variant	1/16	1	NM_147161.4	ENSP00000340260.2	Q8WXI4-2
ACOT11	ENST00000371316.3 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant, splice_region_variant	1/17	1		ENSP00000360366.3	Q8WXI4-1
ACOT11	ENST00000498228.1 linkuse as main transcript	n.122G>A		splice_region_variant, non_coding_transcript_exon_variant	1/8	2
ACOT11	ENST00000481208.5 linkuse as main transcript	n.181+5904G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152178

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000356

AC:

AN:

224468

Hom.:

AF XY:

0.0000248

AC XY:

AN XY:

121182

show subpopulations

Gnomad AFR exome

AF:

0.0000729

Gnomad AMR exome

AF:

0.00

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:

0.0000696

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000380

AC:

AN:

1449116

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

719358

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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:

0.0000572

Gnomad4 NFE exome

AF:

0.0000461

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000165

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

Mar 21, 2024

The c.32G>A (p.R11Q) alteration is located in exon 1 (coding exon 1) of the ACOT11 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the arginine (R) at amino acid position 11 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-0.018

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.054

Sift

Benign

0.64

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.98

D;D

Vest4

0.31

MVP

0.28

MPC

0.22

ClinPred

0.087

GERP RS

2.4

Varity_R

0.048

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00077

dbscSNV1_RF

Benign

0.11

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.

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