chr6-4116002-T-C

Variant names:

• chr6-4116002-T-C
• rs750976196
• NM_206836.3:c.1057A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_206836.3(ECI2):​c.1057A>G​(p.Arg353Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,461,242 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: ECI2 NM_206836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87
• 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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.847

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.1057A>G	p.Arg353Gly	missense	Exon 10 of 10	NP_996667.2	O75521-1
	ECI2	NM_001166010.2		c.967A>G	p.Arg323Gly	missense	Exon 10 of 10	NP_001159482.1	A0A0C4DGA2
	ECI2	NM_006117.3		c.967A>G	p.Arg323Gly	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.1057A>G	p.Arg353Gly	missense	Exon 10 of 10	ENSP00000369461.3	O75521-1
	ECI2	ENST00000361538.6	TSL:1	c.967A>G	p.Arg323Gly	missense	Exon 10 of 10	ENSP00000354737.2	A0A0C4DGA2
	ECI2	ENST00000380125.6	TSL:1	c.967A>G	p.Arg323Gly	missense	Exon 10 of 10	ENSP00000369468.2	A0A0C4DGA2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000361 AC: 9 AN: 249408 AF XY: 0.0000593

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000678 AC: 99 AN: 1461242 Hom.: 0 Cov.: 30 AF XY: 0.0000812 AC XY: 59 AN XY: 726956

African (AFR) AF: 0.0000598 AC: 2 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5758

European-Non Finnish (NFE) AF: 0.0000756 AC: 84 AN: 1111816

Other (OTH) AF: 0.0000663 AC: 4 AN: 60374

GnomAD4 genome Cov.: 33

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000547

EpiControl AF: 0.000178

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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.17
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.9
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.98	D
Vest4		0.78
MutPred		0.54		Loss of MoRF binding (P = 0.0189)
MVP		0.63
MPC		0.43
ClinPred		0.89	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.98
gMVP		0.88
Mutation Taster		=45/55	disease causing

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: rs750976196; hg19: chr6-4116236;