6-4133621-C-A

Variant names:

• chr6-4133621-C-A
• rs3177253
• NM_206836.3:c.141G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. M47V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ECI2 NM_206836.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 43 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0584023).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	NM_206836.3	MANE Select	c.141G>T	p.Met47Ile	missense	Exon 2 of 10	NP_996667.2
	ECI2	NM_001166010.2		c.51G>T	p.Met17Ile	missense	Exon 2 of 10	NP_001159482.1
	ECI2	NM_006117.3		c.51G>T	p.Met17Ile	missense	Exon 2 of 10	NP_006108.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECI2	ENST00000380118.8	TSL:1 MANE Select	c.141G>T	p.Met47Ile	missense	Exon 2 of 10	ENSP00000369461.3
	ECI2	ENST00000361538.6	TSL:1	c.51G>T	p.Met17Ile	missense	Exon 2 of 10	ENSP00000354737.2
	ECI2	ENST00000380125.6	TSL:1	c.51G>T	p.Met17Ile	missense	Exon 2 of 10	ENSP00000369468.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250752 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461568 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727070

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000896 AC: 4 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 22025

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.066
Sift	Benign	0.41	T
Sift4G	Benign	0.47	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	T
GERP RS		4.4
Varity_R		0.15
gMVP		0.25
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs3177253; hg19: chr6-4133855;