ClinVar Miner

Submissions for variant NM_000123.4(ERCC5):c.56C>T (p.Pro19Leu)

gnomAD frequency: 0.00059  dbSNP: rs34291397
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000995079 SCV001149074 uncertain significance not provided 2016-08-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001109705 SCV001267068 uncertain significance Xeroderma pigmentosum, group G 2018-01-13 criteria provided, single submitter clinical testing 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Baylor Genetics RCV001293875 SCV001482537 uncertain significance Cerebrooculofacioskeletal syndrome 3 2020-08-30 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000995079 SCV002010212 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Invitae RCV000995079 SCV002126452 uncertain significance not provided 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 19 of the ERCC5 protein (p.Pro19Leu). This variant is present in population databases (rs34291397, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ERCC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 134159). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002517588 SCV003629056 uncertain significance Inborn genetic diseases 2021-11-25 criteria provided, single submitter clinical testing The c.56C>T (p.P19L) alteration is located in exon 1 (coding exon 1) of the ERCC5 gene. This alteration results from a C to T substitution at nucleotide position 56, causing the proline (P) at amino acid position 19 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV000995079 SCV003921541 uncertain significance not provided 2023-04-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30086788, 29641532, 27498913, 28137924, 24728327, 31937788, 30306255, 33821390)
ITMI RCV000120832 SCV000084997 not provided not specified 2013-09-19 no assertion provided reference population

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