NM_206836.3:c.1150G>A

Variant names:

• chr6-4115909-C-T
• rs143350712
• NM_206836.3:c.1150G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.18
• Publications: 3 publications found

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]

TEX56P (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026037067).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206836.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	NM_206836.3	MANE Select	c.1150G>A	p.Val384Met	missense	Exon 10 of 10	NP_996667.2	O75521-1
	ECI2	NM_001166010.2		c.1060G>A	p.Val354Met	missense	Exon 10 of 10	NP_001159482.1	A0A0C4DGA2
	ECI2	NM_006117.3		c.1060G>A	p.Val354Met	missense	Exon 10 of 10	NP_006108.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	ENST00000380118.8	TSL:1 MANE Select	c.1150G>A	p.Val384Met	missense	Exon 10 of 10	ENSP00000369461.3	O75521-1
	ECI2	ENST00000361538.6	TSL:1	c.1060G>A	p.Val354Met	missense	Exon 10 of 10	ENSP00000354737.2	A0A0C4DGA2
	ECI2	ENST00000380125.6	TSL:1	c.1060G>A	p.Val354Met	missense	Exon 10 of 10	ENSP00000369468.2	A0A0C4DGA2

Frequencies

GnomAD3 genomes AF: 0.000900 AC: 137 AN: 152236 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000753 AC: 189 AN: 251006 AF XY: 0.000700

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 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.: 4 Cov.: 30 AF XY: 0.00132 AC XY: 958 AN XY: 727158

African (AFR) AF: 0.000179 AC: 6 AN: 33464

American (AMR) AF: 0.000806 AC: 36 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000858 AC: 74 AN: 86218

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53412

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00168 AC: 1872 AN: 1111944

Other (OTH) AF: 0.00101 AC: 61 AN: 60396

GnomAD4 genome AF: 0.000899 AC: 137 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.000671 AC XY: 50 AN XY: 74494

African (AFR) AF: 0.000313 AC: 13 AN: 41576

American (AMR) AF: 0.000719 AC: 11 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00154 AC: 105 AN: 68042

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.000903

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000741 AC: 90

EpiCase AF: 0.00120

EpiControl AF: 0.00202

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.44	T
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	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		-2.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.073	T
Polyphen		0.45	B
Vest4		0.14
MVP		0.27
MPC		0.19
ClinPred		0.054	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.24
gMVP		0.53
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs143350712; hg19: chr6-4116143;