Variant 14-73541640-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001037161.2(ACOT1):c.605C>T(p.Thr202Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000926 in 1,242,294 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 4 hom., cov: 17)

Exomes 𝑓: 0.000090 ( 37 hom. )

Consequence

ACOT1
NM_001037161.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016383857).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOT1	NM_001037161.2 link	c.605C>T	p.Thr202Met	missense_variant	Exon 2 of 3	ENST00000311148.9	NP_001032238.1	Q86TX2E9KL42
HEATR4	NM_001220484.1 link	c.-151-11396G>A		intron_variant	Intron 1 of 17	ENST00000553558.6	NP_001207413.1	Q86WZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOT1	ENST00000311148.9 link	c.605C>T	p.Thr202Met	missense_variant	Exon 2 of 3	1	NM_001037161.2	ENSP00000311224.4		Q86TX2
HEATR4	ENST00000553558.6 link	c.-151-11396G>A		intron_variant	Intron 1 of 17	2	NM_001220484.1	ENSP00000450444.2		Q86WZ0

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

110112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000103

Gnomad ASJ

AF:

0.00187

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000116

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

184772

Hom.:

AF XY:

0.0000994

AC XY:

AN XY:

100562

show subpopulations

Gnomad AFR exome

AF:

0.0000721

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00155

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000146

Gnomad OTH exome

AF:

0.000439

GnomAD4 exome

AF:

0.0000901

AC:

102

AN:

1132182

Hom.:

Cov.:

AF XY:

0.0000904

AC XY:

AN XY:

564374

show subpopulations

Gnomad4 AFR exome

AF:

0.0000352

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00159

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000863

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000600

Gnomad4 OTH exome

AF:

0.000218

GnomAD4 genome

AF:

0.000118

AC:

AN:

110112

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

52490

show subpopulations

Gnomad4 AFR

AF:

0.0000306

Gnomad4 AMR

AF:

0.000103

Gnomad4 ASJ

AF:

0.00187

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000116

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000928

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.605C>T (p.T202M) alteration is located in exon 2 (coding exon 2) of the ACOT1 gene. This alteration results from a C to T substitution at nucleotide position 605, causing the threonine (T) at amino acid position 202 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.028

DANN

Benign

0.59

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.020

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.0090

Sift

Benign

0.097

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0060

B;.

Vest4

0.15

MutPred

0.37

Gain of catalytic residue at E201 (P = 0.0211);Gain of catalytic residue at E201 (P = 0.0211);

MVP

0.18

ClinPred

0.030

GERP RS

-7.0

Varity_R

0.019

gMVP

0.28

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