chr13-102873269-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000123.4(ERCC5):c.2890C>T(p.Arg964Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,614,034 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000123.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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ERCC5 | ENST00000652225.2 | c.2890C>T | p.Arg964Trp | missense_variant | Exon 14 of 15 | NM_000123.4 | ENSP00000498881.2 | |||
BIVM-ERCC5 | ENST00000639435.1 | c.4252C>T | p.Arg1418Trp | missense_variant | Exon 24 of 25 | 5 | ENSP00000491742.1 | |||
BIVM-ERCC5 | ENST00000639132.1 | c.3565C>T | p.Arg1189Trp | missense_variant | Exon 23 of 24 | 5 | ENSP00000492684.1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152122Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000497 AC: 125AN: 251442Hom.: 1 AF XY: 0.000714 AC XY: 97AN XY: 135890
GnomAD4 exome AF: 0.000248 AC: 362AN: 1461794Hom.: 2 Cov.: 30 AF XY: 0.000348 AC XY: 253AN XY: 727208
GnomAD4 genome AF: 0.000131 AC: 20AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74442
ClinVar
Submissions by phenotype
not provided Benign:2
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 24728327, 28991257, 26344056) -
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Hereditary cancer-predisposing syndrome Uncertain:1
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Xeroderma pigmentosum, group G Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not specified Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at