dbSNP rs3177253: ECI2:p.Met47Ile (chr6-4133621-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_206836.3(ECI2):c.141G>T(p.Met47Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ECI2
NM_206836.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0584023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECI2	NM_206836.3 link	c.141G>T	p.Met47Ile	missense_variant	Exon 2 of 10	ENST00000380118.8	NP_996667.2	O75521-1
ECI2	NM_001166010.2 link	c.51G>T	p.Met17Ile	missense_variant	Exon 2 of 10		NP_001159482.1	O75521A0A0C4DGA2
ECI2	NM_006117.3 link	c.51G>T	p.Met17Ile	missense_variant	Exon 2 of 10		NP_006108.2	O75521A0A0C4DGA2
ECI2	NR_028588.2 link	n.146G>T		non_coding_transcript_exon_variant	Exon 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECI2	ENST00000380118.8 link	c.141G>T	p.Met47Ile	missense_variant	Exon 2 of 10	1	NM_206836.3	ENSP00000369461.3		O75521-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250752

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0060

T;.;.;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.10

T;.;.;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.058

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.066

Sift

Benign

0.41

T;T;T;T;T

Sift4G

Benign

0.47

T;T;T;T;T

Polyphen

0.0

B;.;.;.;.

Vest4

0.062

MutPred

0.23

Loss of disorder (P = 0.0277);.;.;.;.;

MVP

0.092

MPC

0.068

ClinPred

0.13

GERP RS

4.4

Varity_R

0.15

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over