Variant 6-24697976-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018473.4(ACOT13):c.175T>G(p.Leu59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. L59W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACOT13
NM_018473.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.686

Variant links:

Genes affected

ACOT13 (HGNC:20999): (acyl-CoA thioesterase 13) This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation. The orthologous mouse protein forms a homotetramer and is associated with mitochondria. The mouse protein functions as a medium- and long-chain acyl-CoA thioesterase. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2009]

ACOT13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12166646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOT13	NM_018473.4 linkuse as main transcript	c.175T>G	p.Leu59Val	missense_variant	2/3	ENST00000230048.5
ACOT13	NM_001160094.2 linkuse as main transcript	c.106T>G	p.Leu36Val	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOT13	ENST00000230048.5 linkuse as main transcript	c.175T>G	p.Leu59Val	missense_variant	2/3	1	NM_018473.4	P1	Q9NPJ3-1
ACOT13	ENST00000537591.5 linkuse as main transcript	c.106T>G	p.Leu36Val	missense_variant	3/4	1			Q9NPJ3-2
ACOT13	ENST00000476436.1 linkuse as main transcript	n.386T>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152156

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000876

AC:

1276

AN:

1456322

Hom.:

Cov.:

AF XY:

0.000784

AC XY:

568

AN XY:

724612

show subpopulations

Gnomad4 AFR exome

AF:

0.000749

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.000681

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000722

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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 14, 2023

The c.175T>G (p.L59V) alteration is located in exon 2 (coding exon 2) of the ACOT13 gene. This alteration results from a T to G substitution at nucleotide position 175, causing the leucine (L) at amino acid position 59 to be replaced by a valine (V). 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

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

Cadd

Benign

3.7

Dann

Uncertain

0.99

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.099

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.0068

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.86

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.071

Sift

Benign

0.034

D;T

Sift4G

Benign

0.26

T;T

Polyphen

0.63

.;P

Vest4

0.35

MutPred

0.47

.;Gain of catalytic residue at L59 (P = 0.1278);

MVP

0.18

MPC

0.38

ClinPred

0.17

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.47

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.

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