Genetic Variant NM_001037161.2:c.322G>A (chr14-73537743-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001037161.2(ACOT1):c.322G>A(p.Val108Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000587 in 1,244,230 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00010 ( 4 hom., cov: 19)

Exomes 𝑓: 0.000054 ( 18 hom. )

Consequence

ACOT1
NM_001037161.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.42180055).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037161.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACOT1	NM_001037161.2	MANE Select	c.322G>A	p.Val108Met	missense	Exon 1 of 3	NP_001032238.1	E9KL42
HEATR4	NM_001220484.1	MANE Select	c.-151-7499C>T		intron	N/A	NP_001207413.1	Q86WZ0
HEATR4	NM_203309.2		c.-72-14519C>T		intron	N/A	NP_976054.2	Q86WZ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACOT1	ENST00000311148.9	TSL:1 MANE Select	c.322G>A	p.Val108Met	missense	Exon 1 of 3	ENSP00000311224.4	Q86TX2
ACOT1	ENST00000557556.1	TSL:1	c.322G>A	p.Val108Met	missense	Exon 1 of 3	ENSP00000451764.1	G3V4F2
HEATR4	ENST00000553558.6	TSL:2 MANE Select	c.-151-7499C>T		intron	N/A	ENSP00000450444.2	Q86WZ0

Frequencies

GnomAD3 genomes

AF:

0.000103

AC:

AN:

117054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000840

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:

0.0000189

Gnomad OTH

AF:

0.000636

GnomAD2 exomes

AF:

0.0000736

AC:

AN:

149554

AF XY:

0.000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000285

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000541

AC:

AN:

1127176

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

561160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28722

American (AMR)

AF:

0.000166

AC:

AN:

30204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19808

East Asian (EAS)

AF:

0.00

AC:

AN:

10946

South Asian (SAS)

AF:

0.000232

AC:

AN:

68822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3416

European-Non Finnish (NFE)

AF:

0.0000271

AC:

AN:

885876

Other (OTH)

AF:

0.000349

AC:

AN:

45822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000103

AC:

AN:

117054

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

56286

show subpopulations

African (AFR)

AF:

0.0000277

AC:

AN:

36088

American (AMR)

AF:

0.000840

AC:

AN:

10714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2738

East Asian (EAS)

AF:

0.00

AC:

AN:

1440

South Asian (SAS)

AF:

0.00

AC:

AN:

3752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53034

Other (OTH)

AF:

0.000636

AC:

AN:

1572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.000102

AC:

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

Uncertain

0.50

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.42

MetaSVM

Uncertain

-0.095

MutationAssessor

Pathogenic

4.0

PhyloP100

7.2

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.40

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.38

MutPred

0.69

Gain of catalytic residue at E107 (P = 0.001)

MVP

0.68

ClinPred

0.70

GERP RS

3.8

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.31

gMVP

0.74

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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