rs56255799
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000123.4(ERCC5):c.640C>T(p.Arg214Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,986 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R214H) has been classified as Likely benign.
Frequency
Consequence
NM_000123.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC5 | NM_000123.4 | c.640C>T | p.Arg214Cys | missense_variant | 6/15 | ENST00000652225.2 | |
BIVM-ERCC5 | NM_001204425.2 | c.2002C>T | p.Arg668Cys | missense_variant | 14/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC5 | ENST00000652225.2 | c.640C>T | p.Arg214Cys | missense_variant | 6/15 | NM_000123.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00125 AC: 190AN: 152034Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00282 AC: 709AN: 251296Hom.: 8 AF XY: 0.00315 AC XY: 428AN XY: 135820
GnomAD4 exome AF: 0.00110 AC: 1613AN: 1461834Hom.: 19 Cov.: 31 AF XY: 0.00135 AC XY: 983AN XY: 727222
GnomAD4 genome AF: 0.00126 AC: 191AN: 152152Hom.: 2 Cov.: 32 AF XY: 0.00156 AC XY: 116AN XY: 74370
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Mar 29, 2017 | - - |
Xeroderma pigmentosum, group G;C1851443:Cerebrooculofacioskeletal syndrome 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 16, 2021 | - - |
ERCC5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 29, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Xeroderma pigmentosum, group G Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at