4-5756336-AC-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_153717.3(EVC):โc.1539delโ(p.Glu514ArgfsTer33) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (โ ). Synonymous variant affecting the same amino acid position (i.e. T513T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_153717.3 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC | NM_153717.3 | c.1539del | p.Glu514ArgfsTer33 | frameshift_variant | 11/21 | ENST00000264956.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC | ENST00000264956.11 | c.1539del | p.Glu514ArgfsTer33 | frameshift_variant | 11/21 | 1 | NM_153717.3 | P1 | |
EVC | ENST00000509451.1 | c.1539del | p.Glu514ArgfsTer11 | frameshift_variant | 11/12 | 1 | |||
CRMP1 | ENST00000506216.5 | n.1648-8025del | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459512Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4AN XY: 725618
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Ellis-van Creveld syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2017 | This sequence change creates a premature translational stop signal (p.Glu514Argfs*33) in the EVC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EVC-related disease. Loss-of-function variants in EVC are known to be pathogenic (PMID: 23220543). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | Mar 08, 2017 | - - |
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | This sequence change creates a premature translational stop signal (p.Glu514Argfs*33) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EVC-related conditions. ClinVar contains an entry for this variant (Variation ID: 455998). 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