rs121917902
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The ENST00000355832.10(ERCC6):c.1357C>T(p.Arg453Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,566 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R453R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000355832.10 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ERCC6 | NM_000124.4 | c.1357C>T | p.Arg453Ter | stop_gained | 5/21 | ENST00000355832.10 | NP_000115.1 | |
ERCC6 | NM_001277058.2 | c.1357C>T | p.Arg453Ter | stop_gained | 5/6 | ENST00000447839.7 | NP_001263987.1 | |
PGBD3 | NM_170753.3 | c.-48C>T | 5_prime_UTR_variant | 1/2 | NP_736609.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERCC6 | ENST00000355832.10 | c.1357C>T | p.Arg453Ter | stop_gained | 5/21 | 1 | NM_000124.4 | ENSP00000348089 | P1 | |
ERCC6 | ENST00000447839.7 | c.1357C>T | p.Arg453Ter | stop_gained | 5/6 | 2 | NM_001277058.2 | ENSP00000387966 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461566Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727112
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cockayne syndrome type 2 Pathogenic:3
Pathogenic, criteria provided, single submitter | research | Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Claritas Genomics | Jul 29, 2013 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 1999 | - - |
Cerebrooculofacioskeletal syndrome 1;C0265201:DE SANCTIS-CACCHIONE SYNDROME;C0751038:Cockayne syndrome type 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Oct 12, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 21, 2024 | This sequence change creates a premature translational stop signal (p.Arg453*) in the ERCC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 18628313, 29572252). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Cockayne syndrome (PMID: 9443879, 29572252). ClinVar contains an entry for this variant (Variation ID: 1703). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Cerebrooculofacioskeletal syndrome 1;C0265201:DE SANCTIS-CACCHIONE SYNDROME;C0684249:Lung carcinoma;C0751038:Cockayne syndrome type 2;C3151063:Age related macular degeneration 5;C3551173:UV-sensitive syndrome 1;C4310783:Premature ovarian failure 11 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at