Variant 1-54597295-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_147161.4(ACOT11):c.644C>A(p.Ala215Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ACOT11
NM_147161.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61

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:

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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/exons	MANE	Protein	UniProt
ACOT11	NM_147161.4 linkuse as main transcript	c.644C>A	p.Ala215Asp	missense_variant	7/16	ENST00000343744.7	NP_671517.1	Q8WXI4-2
ACOT11	NM_015547.4 linkuse as main transcript	c.644C>A	p.Ala215Asp	missense_variant	7/17		NP_056362.1	Q8WXI4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOT11	ENST00000343744.7 linkuse as main transcript	c.644C>A	p.Ala215Asp	missense_variant	7/16	1	NM_147161.4	ENSP00000340260.2		Q8WXI4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726970

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 17, 2024

The c.644C>A (p.A215D) alteration is located in exon 7 (coding exon 7) of the ACOT11 gene. This alteration results from a C to A substitution at nucleotide position 644, causing the alanine (A) at amino acid position 215 to be replaced by an aspartic acid (D). 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

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

0.043

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

M;M

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.14

T;T

Polyphen

0.093

B;B

Vest4

0.88

MutPred

0.42

Gain of disorder (P = 0.0379);Gain of disorder (P = 0.0379);

MVP

0.51

MPC

0.62

ClinPred

0.99

GERP RS

5.0

Varity_R

0.55

gMVP

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over