rs121434573
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3_ModeratePP5
The NM_000123.4(ERCC5):c.526C>T(p.Gln176Ter) variant causes a stop gained, splice region change. The variant allele was found at a frequency of 0.00000124 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Q176Q) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000123.4 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC5 | NM_000123.4 | c.526C>T | p.Gln176Ter | stop_gained, splice_region_variant | 5/15 | ENST00000652225.2 | |
BIVM-ERCC5 | NM_001204425.2 | c.1888C>T | p.Gln630Ter | stop_gained, splice_region_variant | 13/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC5 | ENST00000652225.2 | c.526C>T | p.Gln176Ter | stop_gained, splice_region_variant | 5/15 | NM_000123.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460756Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726774
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
Xeroderma pigmentosum group G/Cockayne syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2001 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at