Genetic Variant ECI2:p.Val384Met (chr6-4115909-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_206836.3(ECI2):c.1150G>A(p.Val384Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,614,060 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

ECI2
NM_206836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.18

Variant links:

Genes affected

ECI2 (HGNC:14601): (enoyl-CoA delta isomerase 2) This gene encodes a member of the hydratase/isomerase superfamily. The protein encoded is a key mitochondrial enzyme involved in beta-oxidation of unsaturated fatty acids. It catalyzes the transformation of 3-cis and 3-trans-enoyl-CoA esters arising during the stepwise degradation of cis-, mono-, and polyunsaturated fatty acids to the 2-trans-enoyl-CoA intermediates. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2011]

ECI2 links:

TEX56P (HGNC:21620): (testis expressed 56, pseudogene)

TEX56P 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=0.026037067).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECI2	NM_206836.3 link	c.1150G>A	p.Val384Met	missense_variant	Exon 10 of 10	ENST00000380118.8	NP_996667.2	O75521-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECI2	ENST00000380118.8 link	c.1150G>A	p.Val384Met	missense_variant	Exon 10 of 10	1	NM_206836.3	ENSP00000369461.3		O75521-1

Frequencies

GnomAD3 genomes

AF:

0.000900

AC:

137

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000753

AC:

189

AN:

251006

Hom.:

AF XY:

0.000700

AC XY:

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000589

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.00140

AC:

2052

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

958

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000806

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000858

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000899

AC:

137

AN:

152354

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000903

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000741

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00202

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1150G>A (p.V384M) alteration is located in exon 10 (coding exon 10) of the ECI2 gene. This alteration results from a G to A substitution at nucleotide position 1150, causing the valine (V) at amino acid position 384 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

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

3.0

DANN

Uncertain

0.97

DEOGEN2

Benign

0.015

T;.;.;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.037

LIST_S2

Uncertain

0.93

D;.;.;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.026

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

L;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Benign

0.073

T;T;T;T

Polyphen

0.45

B;.;.;.

Vest4

0.14

MVP

0.27

MPC

0.19

ClinPred

0.054

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.24

gMVP

0.53

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