10-11749516-C-T

Variant names:

• chr10-11749516-C-T
• NM_024693.5:c.314C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024693.5(ECHDC3):​c.314C>T​(p.Ser105Phe) variant causes a missense change involving the alteration of a 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: 32)
• Consequence: ECHDC3 NM_024693.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECHDC3	NM_024693.5	c.314C>T	p.Ser105Phe	missense_variant	Exon 3 of 5	ENST00000379215.9	NP_078969.3
ECHDC3	XM_047425750.1	c.473C>T	p.Ser158Phe	missense_variant	Exon 3 of 5		XP_047281706.1
ECHDC3	XM_011519689.1	c.314C>T	p.Ser105Phe	missense_variant	Exon 3 of 4		XP_011517991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECHDC3	ENST00000379215.9	c.314C>T	p.Ser105Phe	missense_variant	Exon 3 of 5	1	NM_024693.5	ENSP00000368517.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.314C>T (p.S105F) alteration is located in exon 3 (coding exon 3) of the ECHDC3 gene. This alteration results from a C to T substitution at nucleotide position 314, causing the serine (S) at amino acid position 105 to be replaced by a phenylalanine (F). 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	0.61
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	3.1	M;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.88
MutPred		0.78		Loss of disorder (P = 0.0057);.;.;
MVP		0.66
MPC		0.38
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.95
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-11791515;