rs786205176
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000082.4(ERCC8):c.141del(p.Asn47LysfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
ERCC8
NM_000082.4 frameshift
NM_000082.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.24
Genes affected
ERCC8 (HGNC:3439): (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-60928895-TG-T is Pathogenic according to our data. Variant chr5-60928895-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 190175.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC8 | NM_000082.4 | c.141del | p.Asn47LysfsTer21 | frameshift_variant | 2/12 | ENST00000676185.1 | |
ERCC8 | NM_001007234.3 | c.141del | p.Asn47LysfsTer21 | frameshift_variant | 2/6 | ||
ERCC8 | NM_001007233.3 | c.-252del | 5_prime_UTR_variant | 2/13 | |||
ERCC8 | NM_001290285.2 | c.-237del | 5_prime_UTR_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC8 | ENST00000676185.1 | c.141del | p.Asn47LysfsTer21 | frameshift_variant | 2/12 | NM_000082.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cockayne syndrome type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Claritas Genomics | Mar 15, 2012 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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