GeneBe

rs1553567402

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5

The NM_004826.4(ECEL1):​c.1221_1223delGGT​(p.Val408del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000000685 in 1,460,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ECEL1
NM_004826.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.12
Variant links:
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 6 ACMG points.

PM1
In a disulfide_bond (size 254) in uniprot entity ECEL1_HUMAN there are 10 pathogenic changes around while only 3 benign (77%) in NM_004826.4
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_004826.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 2-232484184-GACC-G is Pathogenic according to our data. Variant chr2-232484184-GACC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ECEL1NM_004826.4 linkc.1221_1223delGGT p.Val408del disruptive_inframe_deletion Exon 7 of 18 ENST00000304546.6 NP_004817.2 O95672-1A0A6F7YIA8
ECEL1NM_001290787.2 linkc.1221_1223delGGT p.Val408del disruptive_inframe_deletion Exon 7 of 18 NP_001277716.1 O95672-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ECEL1ENST00000304546.6 linkc.1221_1223delGGT p.Val408del disruptive_inframe_deletion Exon 7 of 18 1 NM_004826.4 ENSP00000302051.1 O95672-1
ECEL1ENST00000409941.1 linkc.1221_1223delGGT p.Val408del disruptive_inframe_deletion Exon 6 of 17 1 ENSP00000386333.1 O95672-2
ECEL1ENST00000482346.1 linkn.1532_1534delGGT non_coding_transcript_exon_variant Exon 6 of 17 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460890
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
726742
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr2-233348894; API