rs878853117
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_004826.4(ECEL1):āc.869A>Gā(p.Tyr290Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,100 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 Pathogenic (no stars).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 34)
Consequence
ECEL1
NM_004826.4 missense
NM_004826.4 missense
Scores
14
4
1
Clinical Significance
Conservation
PhyloP100: 4.00
Genes affected
ECEL1 (HGNC:3147): (endothelin converting enzyme like 1) This gene encodes a member of the M13 family of endopeptidases. Members of this family are zinc-containing type II integral-membrane proteins that are important regulators of neuropeptide and peptide hormone activity. Mutations in this gene are associated with autosomal recessive distal arthrogryposis, type 5D. This gene has multiple pseudogenes on chromosome 2. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.983
PP5
?
Variant 2-232485078-T-C is Pathogenic according to our data. Variant chr2-232485078-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 242403.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-232485078-T-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ECEL1 | NM_004826.4 | c.869A>G | p.Tyr290Cys | missense_variant | 4/18 | ENST00000304546.6 | |
ECEL1 | NM_001290787.2 | c.869A>G | p.Tyr290Cys | missense_variant | 4/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ECEL1 | ENST00000304546.6 | c.869A>G | p.Tyr290Cys | missense_variant | 4/18 | 1 | NM_004826.4 | P4 | |
ECEL1 | ENST00000409941.1 | c.869A>G | p.Tyr290Cys | missense_variant | 3/17 | 1 | A1 | ||
ECEL1 | ENST00000482346.1 | n.1180A>G | non_coding_transcript_exon_variant | 3/17 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 34
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GnomAD4 exome Cov.: 60
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74294
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Distal arthrogryposis type 5D Pathogenic:1
Pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Jan 08, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of catalytic residue at Y290 (P = 0.0492);Loss of catalytic residue at Y290 (P = 0.0492);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at