chr6-4115937-T-A

Variant names:

• chr6-4115937-T-A
• NM_206836.3:c.1122A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_206836.3(ECI2):​c.1122A>T​(p.Arg374Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ECI2 NM_206836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.992
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECI2	NM_206836.3	c.1122A>T	p.Arg374Ser	missense_variant	Exon 10 of 10	ENST00000380118.8	NP_996667.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECI2	ENST00000380118.8	c.1122A>T	p.Arg374Ser	missense_variant	Exon 10 of 10	1	NM_206836.3	ENSP00000369461.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1122A>T (p.R374S) alteration is located in exon 10 (coding exon 10) of the ECI2 gene. This alteration results from a A to T substitution at nucleotide position 1122, causing the arginine (R) at amino acid position 374 to be replaced by a serine (S). 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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	16
DANN	Uncertain	0.97
DEOGEN2	Benign	0.064	T;.;.;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.75	T;.;.;T
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.5	M;.;.;.
PhyloP100		-0.99
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.3	D;D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.020	D;D;D;D
Polyphen		0.97	D;.;.;.
Vest4		0.77
MutPred		0.59		Loss of stability (P = 0.0949);.;.;.;
MVP		0.42
MPC		0.40
ClinPred		0.99	D
GERP RS		-6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.84
Mutation Taster		=62/38	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

hg19: chr6-4116171;