ECE1 p.Asp547Asp

Variant names:

• chr1-21233586-G-G
• NM_001397.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-21233587--
• chr1-21233587-A-G

Variant summary

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

The NM_001397.3(ECE1):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECE1 NM_001397.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 0 publications found

Genes affected

ECE1 (HGNC:3146): (endothelin converting enzyme 1) The protein encoded by this gene is involved in proteolytic processing of endothelin precursors to biologically active peptides. Mutations in this gene are associated with Hirschsprung disease, cardiac defects and autonomic dysfunction. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Sep 2009]

ECE1 Gene-Disease associations (from GenCC):

• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001397.3. 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
	ECE1	NM_001397.3	MANE Select	c.		exon_region	Exon 14 of 19	NP_001388.1	P42892-1
	ECE1	NM_001113349.2		c.		exon_region	Exon 13 of 18	NP_001106820.1	P42892-4
	ECE1	NM_001113347.2		c.		exon_region	Exon 12 of 17	NP_001106818.1	P42892-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	ENST00000374893.11	TSL:1 MANE Select	c.		exon_region	Exon 14 of 19	ENSP00000364028.6	P42892-1
	ECE1	ENST00000264205.10	TSL:1	c.		exon_region	Exon 13 of 18	ENSP00000264205.6	P42892-4
	ECE1	ENST00000357071.8	TSL:1	c.		exon_region	Exon 12 of 17	ENSP00000349581.4	P42892-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-21560079;