4-5729369-C-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_153717.3(EVC):c.363C>A(p.Tyr121*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,860 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_153717.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EVC | NM_153717.3 | c.363C>A | p.Tyr121* | stop_gained | 3/21 | ENST00000264956.11 | NP_714928.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EVC | ENST00000264956.11 | c.363C>A | p.Tyr121* | stop_gained | 3/21 | 1 | NM_153717.3 | ENSP00000264956.6 | ||
EVC | ENST00000509451.1 | c.363C>A | p.Tyr121* | stop_gained | 3/12 | 1 | ENSP00000426774.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251482Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727228
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Ellis-van Creveld syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 02, 2017 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 09, 2020 | - - |
Short-rib thoracic dysplasia 6 with or without polydactyly Pathogenic:2
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 21, 2023 | This sequence change creates a premature translational stop signal (p.Tyr121*) in the EVC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EVC are known to be pathogenic (PMID: 23220543). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Ellis–van Creveld syndrome or short-rib polydactyly syndrome type II (PMID: 19810119, 29068549). ClinVar contains an entry for this variant (Variation ID: 446662). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at