Genetic Variant ACOT4:p.Pro89Ala (chr14-73592224-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152331.4(ACOT4):c.265C>G(p.Pro89Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P89T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACOT4
NM_152331.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

Publications

0 publications found

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:

ENSG00000288797 (HGNC:):

ENSG00000288797 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13588423).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152331.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT4	NM_152331.4	MANE Select	c.265C>G	p.Pro89Ala	missense	Exon 1 of 3	NP_689544.3	Q8N9L9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACOT4	ENST00000326303.5	TSL:1 MANE Select	c.265C>G	p.Pro89Ala	missense	Exon 1 of 3	ENSP00000323071.4	Q8N9L9
ENSG00000288797	ENST00000686335.1		n.86C>G		non_coding_transcript_exon	Exon 1 of 2
ENSG00000258603	ENST00000664243.1		n.63-34252G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460758

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111420

Other (OTH)

AF:

0.00

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.078

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.70

M_CAP

Benign

0.029

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.7

PhyloP100

1.6

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.17

Sift

Benign

0.33

Sift4G

Benign

0.29

Polyphen

0.21

Vest4

0.21

MutPred

0.56

Gain of helix (P = 0.0078)

MVP

0.61

MPC

0.26

ClinPred

0.83

GERP RS

4.0

PromoterAI

-0.0015

Neutral

(source)

Varity_R

0.47

gMVP

0.38

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over