Variant 14-73593804-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_152331.4(ACOT4):c.560C>A(p.Ala187Asp) variant causes a missense change. The variant allele was found at a frequency of 0.186 in 1,607,944 control chromosomes in the GnomAD database, including 32,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2210 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29806 hom. )

Consequence

ACOT4
NM_152331.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.17

Variant links:

Genes affected

ACOT4 (HGNC:19748): (acyl-CoA thioesterase 4) Enables acyl-CoA hydrolase activity and succinyl-CoA hydrolase activity. Involved in carboxylic acid metabolic process; saturated monocarboxylic acid metabolic process; and succinyl-CoA metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACOT4 links:

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

HEATR4 links:

ENSG00000258603 (HGNC:):

ENSG00000258603 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026230812).

BP6

Variant 14-73593804-C-A is Benign according to our data. Variant chr14-73593804-C-A is described in ClinVar as [Benign]. Clinvar id is 2798877.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOT4	NM_152331.4 link	c.560C>A	p.Ala187Asp	missense_variant	Exon 2 of 3	ENST00000326303.5	NP_689544.3	Q8N9L9
HEATR4	XM_047431370.1 link	c.-73+39857G>T		intron_variant	Intron 1 of 16		XP_047287326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACOT4	ENST00000326303.5 link	c.560C>A	p.Ala187Asp	missense_variant	Exon 2 of 3	1	NM_152331.4	ENSP00000323071.4	Q8N9L9
ENSG00000258603	ENST00000664243.1 link	n.63-35832G>T		intron_variant	Intron 1 of 1
ENSG00000288797	ENST00000686335.1 link	n.279-1245C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22370

AN:

152052

Hom.:

2209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.0652

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.0495

AC:

10293

AN:

207986

Hom.:

1840

AF XY:

0.0491

AC XY:

5490

AN XY:

111854

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.0319

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.0743

Gnomad OTH exome

AF:

0.0452

GnomAD4 exome

AF:

0.190

AC:

277149

AN:

1455774

Hom.:

29806

Cov.:

AF XY:

0.186

AC XY:

134915

AN XY:

723760

show subpopulations

Gnomad4 AFR exome

AF:

0.0453

Gnomad4 AMR exome

AF:

0.0867

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0723

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.147

AC:

22371

AN:

152170

Hom.:

2210

Cov.:

AF XY:

0.145

AC XY:

10827

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0523

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.0654

Gnomad4 FIN

AF:

0.260

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.0376

Hom.:

770

Bravo

AF:

0.133

ESP6500AA

AF:

0.0172

AC:

ESP6500EA

AF:

0.0974

AC:

837

ExAC

AF:

0.128

AC:

15546

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.7

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.33

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.34

MPC

1.1

ClinPred

0.074

GERP RS

5.3

Varity_R

0.95

gMVP

0.95

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