Genetic Variant ENST00000613168.1:c.3G>A (chr14-73569303-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The ENST00000613168.1(ACOT2):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACOT2
ENST00000613168.1 start_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0560

Publications

0 publications found

Variant links:

Genes affected

ACOT2 (HGNC:18431): (acyl-CoA thioesterase 2) This gene encodes a member of the acyl-CoA thioesterase protein family, and is one of four acyl-CoA hydrolase genes located in a cluster on chromosome 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACOT2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 43 codons. Genomic position: 73569427. Lost 0.091 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000613168.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACOT2	NM_006821.6	MANE Select	c.63G>A	p.Met21Ile	missense	Exon 1 of 3	NP_006812.3
ACOT2	NM_001364178.1		c.63G>A	p.Met21Ile	missense	Exon 1 of 3	NP_001351107.1
ACOT2	NM_001364177.1		c.-42G>A		5_prime_UTR	Exon 1 of 3	NP_001351106.1	B3KSA0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACOT2	ENST00000613168.1	TSL:1	c.3G>A	p.Met1?	start_lost	Exon 1 of 3	ENSP00000477685.1	A0A087WT95
ACOT2	ENST00000238651.10	TSL:1 MANE Select	c.63G>A	p.Met21Ile	missense	Exon 1 of 3	ENSP00000238651.5	P49753-1
ACOT2	ENST00000864002.1		c.63G>A	p.Met21Ile	missense	Exon 1 of 3	ENSP00000534061.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111794

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.9

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.011

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.33

M_CAP

Benign

0.0051

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.056

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.61

REVEL

Benign

0.025

Sift

Benign

0.036

Sift4G

Benign

0.12

Polyphen

0.017

Vest4

0.12

MutPred

0.29

Gain of sheet (P = 0.0149)

MVP

0.24

ClinPred

0.028

GERP RS

1.1

PromoterAI

-0.90

Under-expression

(source)

Varity_R

0.17

gMVP

0.23

Mutation Taster

=300/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over