Genetic Variant NM_152331.4:c.265C>A (chr14-73592224-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_152331.4(ACOT4):c.265C>A(p.Pro89Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ACOT4
NM_152331.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29416102).

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>A	p.Pro89Thr	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>A	p.Pro89Thr	missense	Exon 1 of 3	ENSP00000323071.4	Q8N9L9
ENSG00000288797	ENST00000686335.1		n.86C>A		non_coding_transcript_exon	Exon 1 of 2
ENSG00000258603	ENST00000664243.1		n.63-34252G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000283

AC:

AN:

246988

AF XY:

0.0000298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460758

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.000269

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:

9.00e-7

AC:

AN:

1111420

Other (OTH)

AF:

0.00

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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

AF:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41464

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.081

MetaRNN

Benign

0.29

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

3.1

PhyloP100

1.6

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.1

REVEL

Uncertain

0.42

Sift

Benign

0.035

Sift4G

Benign

0.20

Polyphen

0.99

Vest4

0.20

MutPred

0.53

Gain of helix (P = 0.027)

MVP

0.74

MPC

0.33

ClinPred

0.53

GERP RS

4.0

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.73

gMVP

0.49

Mutation Taster

=91/9

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