Variant 14-73537506-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000311148.9(ACOT1):c.85G>A(p.Glu29Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 1,215,596 control chromosomes in the GnomAD database, including 3,434 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 175 hom., cov: 20)

Exomes 𝑓: 0.0096 ( 3259 hom. )

Consequence

ACOT1
ENST00000311148.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.150

Variant links:

Genes affected

ACOT1 (HGNC:33128): (acyl-CoA thioesterase 1) Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACOT1 links:

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009623647).

BP6

Variant 14-73537506-G-A is Benign according to our data. Variant chr14-73537506-G-A is described in ClinVar as [Benign]. Clinvar id is 3067179.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 175 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOT1	NM_001037161.2 linkuse as main transcript	c.85G>A	p.Glu29Lys	missense_variant	1/3	ENST00000311148.9	NP_001032238.1
HEATR4	NM_001220484.1 linkuse as main transcript	c.-151-7262C>T		intron_variant		ENST00000553558.6	NP_001207413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOT1	ENST00000311148.9 linkuse as main transcript	c.85G>A	p.Glu29Lys	missense_variant	1/3	1	NM_001037161.2	ENSP00000311224	P1
HEATR4	ENST00000553558.6 linkuse as main transcript	c.-151-7262C>T		intron_variant		2	NM_001220484.1	ENSP00000450444	P1

Frequencies

GnomAD3 genomes

AF:

0.00491

AC:

580

AN:

118110

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00485

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.000365

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000856

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00886

Gnomad OTH

AF:

0.00754

GnomAD3 exomes

AF:

0.00586

AC:

616

AN:

105042

Hom.:

192

AF XY:

0.00565

AC XY:

327

AN XY:

57874

show subpopulations

Gnomad AFR exome

AF:

0.000339

Gnomad AMR exome

AF:

0.00627

Gnomad ASJ exome

AF:

0.000666

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000214

Gnomad FIN exome

AF:

0.00169

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00852

GnomAD4 exome

AF:

0.00958

AC:

10511

AN:

1097424

Hom.:

3259

Cov.:

AF XY:

0.00918

AC XY:

4987

AN XY:

543534

show subpopulations

Gnomad4 AFR exome

AF:

0.00107

Gnomad4 AMR exome

AF:

0.00624

Gnomad4 ASJ exome

AF:

0.000466

Gnomad4 EAS exome

AF:

0.000195

Gnomad4 SAS exome

AF:

0.000532

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.00989

GnomAD4 genome

AF:

0.00491

AC:

580

AN:

118172

Hom.:

175

Cov.:

AF XY:

0.00393

AC XY:

224

AN XY:

56978

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.000365

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000856

Gnomad4 NFE

AF:

0.00887

Gnomad4 OTH

AF:

0.00743

Alfa

AF:

0.00215

Hom.:

ExAC

AF:

0.00367

AC:

286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

ACOT1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.11

Sift

Benign

0.80

T;T

Sift4G

Benign

0.88

T;T

Polyphen

0.026

B;.

Vest4

0.10

MVP

0.63

ClinPred

0.0055

GERP RS

0.39

Varity_R

0.15

gMVP

0.40

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