rs1047769
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000123.4(ERCC5):āc.760A>Gā(p.Met254Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 1,614,194 control chromosomes in the GnomAD database, including 1,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.025 ( 61 hom., cov: 32)
Exomes š: 0.035 ( 1047 hom. )
Consequence
ERCC5
NM_000123.4 missense
NM_000123.4 missense
Scores
6
5
Clinical Significance
Conservation
PhyloP100: 2.92
Genes affected
ERCC5 (HGNC:3437): (ERCC excision repair 5, endonuclease) This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0047145486).
BP6
?
Variant 13-102861594-A-G is Benign according to our data. Variant chr13-102861594-A-G is described in ClinVar as [Benign]. Clinvar id is 129012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-102861594-A-G is described in Lovd as [Benign]. Variant chr13-102861594-A-G is described in Lovd as [Likely_benign].
BA1
?
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC5 | NM_000123.4 | c.760A>G | p.Met254Val | missense_variant | 7/15 | ENST00000652225.2 | |
BIVM-ERCC5 | NM_001204425.2 | c.2122A>G | p.Met708Val | missense_variant | 15/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC5 | ENST00000652225.2 | c.760A>G | p.Met254Val | missense_variant | 7/15 | NM_000123.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0254 AC: 3870AN: 152230Hom.: 61 Cov.: 32
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GnomAD3 exomes AF: 0.0299 AC: 7516AN: 251364Hom.: 163 AF XY: 0.0330 AC XY: 4481AN XY: 135846
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GnomAD4 exome AF: 0.0352 AC: 51401AN: 1461846Hom.: 1047 Cov.: 31 AF XY: 0.0359 AC XY: 26125AN XY: 727224
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GnomAD4 genome ? AF: 0.0254 AC: 3871AN: 152348Hom.: 61 Cov.: 32 AF XY: 0.0251 AC XY: 1868AN XY: 74494
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ClinVar
Significance: Benign
Submissions summary: Benign:7Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Xeroderma pigmentosum, group G Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | May 08, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
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 Benign:2Other:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
Polyphen
0.86
.;.;.;P
Vest4
0.22
MPC
0.38
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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