Genetic Variant ECHDC3:p.Arg51Trp (chr10-11742727-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024693.5(ECHDC3):c.151C>T(p.Arg51Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,234,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ECHDC3
NM_024693.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.811

Variant links:

Genes affected

ECHDC3 (HGNC:23489): (enoyl-CoA hydratase domain containing 3) Predicted to enable enoyl-CoA hydratase activity. Involved in positive regulation of cellular response to insulin stimulus. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ECHDC3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20623672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECHDC3	NM_024693.5 link	c.151C>T	p.Arg51Trp	missense_variant	Exon 1 of 5	ENST00000379215.9	NP_078969.3	Q96DC8-1A0A140VKF9
ECHDC3	XM_047425750.1 link	c.151C>T	p.Arg51Trp	missense_variant	Exon 1 of 5		XP_047281706.1
ECHDC3	XM_011519689.1 link	c.151C>T	p.Arg51Trp	missense_variant	Exon 1 of 4		XP_011517991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ECHDC3	ENST00000379215.9 link	c.151C>T	p.Arg51Trp	missense_variant	Exon 1 of 5	1	NM_024693.5	ENSP00000368517.4	Q96DC8-1
ECHDC3	ENST00000496136.5 link	n.362C>T		non_coding_transcript_exon_variant	Exon 1 of 6	1
ECHDC3	ENST00000420401.5 link	c.151C>T	p.Arg51Trp	missense_variant	Exon 1 of 4	2		ENSP00000405584.1	Q5W0J8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000554

AC:

AN:

1082080

Hom.:

Cov.:

AF XY:

0.00000585

AC XY:

AN XY:

512654

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000117

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000217

Gnomad4 OTH exome

AF:

0.0000231

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.151C>T (p.R51W) alteration is located in exon 1 (coding exon 1) of the ECHDC3 gene. This alteration results from a C to T substitution at nucleotide position 151, causing the arginine (R) at amino acid position 51 to be replaced by a tryptophan (W). 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

Benign

0.086

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.040

Sift

Benign

0.036

D;T

Sift4G

Uncertain

0.043

D;T

Polyphen

0.26

B;.

Vest4

0.21

MutPred

0.45

Loss of disorder (P = 0.0073);Loss of disorder (P = 0.0073);

MVP

0.41

MPC

0.069

ClinPred

0.56

GERP RS

1.2

Varity_R

0.35

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over