6-4117396-T-C

Variant names:

• chr6-4117396-T-C
• NM_206836.3:c.941A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206836.3(ECI2):​c.941A>G​(p.Gln314Arg) 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 benign outcome for this variant. 17/22 in silico tools predict a benign 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: 0.378
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15663621).

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.941A>G	p.Gln314Arg	missense	Exon 9 of 10	NP_996667.2	O75521-1
	ECI2	NM_001166010.2		c.851A>G	p.Gln284Arg	missense	Exon 9 of 10	NP_001159482.1	A0A0C4DGA2
	ECI2	NM_006117.3		c.851A>G	p.Gln284Arg	missense	Exon 9 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.941A>G	p.Gln314Arg	missense	Exon 9 of 10	ENSP00000369461.3	O75521-1
	ECI2	ENST00000361538.6	TSL:1	c.851A>G	p.Gln284Arg	missense	Exon 9 of 10	ENSP00000354737.2	A0A0C4DGA2
	ECI2	ENST00000380125.6	TSL:1	c.851A>G	p.Gln284Arg	missense	Exon 9 of 10	ENSP00000369468.2	A0A0C4DGA2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.082
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.78	N
PhyloP100		0.38
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.039
Sift	Benign	0.41	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.47		Gain of methylation at Q314 (P = 0.0075)
MVP		0.29
MPC		0.066
ClinPred		0.087	T
GERP RS		0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.068
gMVP		0.60
Mutation Taster		=85/15	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: chr6-4117630;