Variant X-23722697-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001037171.2(ACOT9):c.457A>G(p.Ile153Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000725 in 1,199,758 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 10 hem., cov: 22)

Exomes 𝑓: 0.000056 ( 0 hom. 17 hem. )

Consequence

ACOT9
NM_001037171.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Variant links:

Genes affected

ACOT9 (HGNC:17152): (acyl-CoA thioesterase 9) The protein encoded by this gene is a mitochondrial acyl-CoA thioesterase of unknown function. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACOT9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10797089).

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACOT9	NM_001037171.2 linkuse as main transcript	c.457A>G	p.Ile153Val	missense_variant	7/16	ENST00000379303.10
ACOT9	NM_001033583.3 linkuse as main transcript	c.430A>G	p.Ile144Val	missense_variant	6/15
ACOT9	NM_001330259.2 linkuse as main transcript	c.250A>G	p.Ile84Val	missense_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOT9	ENST00000379303.10 linkuse as main transcript	c.457A>G	p.Ile153Val	missense_variant	7/16	1	NM_001037171.2	A2	Q9Y305-4

Frequencies

GnomAD3 genomes

AF:

0.000242

AC:

AN:

111598

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

33826

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00202

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:

0.0000940

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.000113

AC:

AN:

177759

Hom.:

AF XY:

0.0000320

AC XY:

AN XY:

62417

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000497

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:

0.0000623

Gnomad OTH exome

AF:

0.000460

GnomAD4 exome

AF:

0.0000561

AC:

AN:

1088108

Hom.:

Cov.:

AF XY:

0.0000479

AC XY:

AN XY:

354992

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000516

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:

0.0000419

Gnomad4 OTH exome

AF:

0.0000656

GnomAD4 genome

AF:

0.000233

AC:

AN:

111650

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

33888

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00202

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.000659

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000238

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

Dec 02, 2021

The c.457A>G (p.I153V) alteration is located in exon 7 (coding exon 7) of the ACOT9 gene. This alteration results from a A to G substitution at nucleotide position 457, causing the isoleucine (I) at amino acid position 153 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

0.073

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.82

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.079

T;T;T;T

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.87

P;P;.;.

Vest4

0.45

MVP

0.26

MPC

0.35

ClinPred

0.11

GERP RS

5.3

Varity_R

0.33

gMVP

0.54

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