13-102853836-AAAGAC-A
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000123.4(ERCC5):c.348_352delACAAG(p.Arg116SerfsTer12) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ERCC5
NM_000123.4 frameshift
NM_000123.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.36
Publications
0 publications found
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]
BIVM-ERCC5 (HGNC:43690): (BIVM-ERCC5 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BIVM (basic, immunoglobulin-like variable motif containing) and ERCC5 (excision repair cross-complementing rodent repair deficiency, complementation group 5) genes on chromosome 13. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Feb 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 13-102853836-AAAGAC-A is Pathogenic according to our data. Variant chr13-102853836-AAAGAC-A is described in ClinVar as [Pathogenic]. Clinvar id is 522981.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ERCC5 | NM_000123.4 | c.348_352delACAAG | p.Arg116SerfsTer12 | frameshift_variant | Exon 3 of 15 | ENST00000652225.2 | NP_000114.3 | |
| BIVM-ERCC5 | NM_001204425.2 | c.1710_1714delACAAG | p.Arg570SerfsTer12 | frameshift_variant | Exon 11 of 23 | NP_001191354.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ERCC5 | ENST00000652225.2 | c.348_352delACAAG | p.Arg116SerfsTer12 | frameshift_variant | Exon 3 of 15 | NM_000123.4 | ENSP00000498881.2 | |||
| BIVM-ERCC5 | ENST00000639435.1 | c.1710_1714delACAAG | p.Arg570SerfsTer12 | frameshift_variant | Exon 13 of 25 | 5 | ENSP00000491742.1 | |||
| BIVM-ERCC5 | ENST00000639132.1 | c.1023_1027delACAAG | p.Arg341SerfsTer12 | frameshift_variant | Exon 12 of 24 | 5 | ENSP00000492684.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251320 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251320
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
AF:
Gnomad ASJ exome
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Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461876Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727238 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1461876
Hom.:
AF XY:
AC XY:
2
AN XY:
727238
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39692
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1112008
Other (OTH)
AF:
AC:
1
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Xeroderma pigmentosum-Cockayne syndrome complex Pathogenic:1
Dec 18, 2017
Genomic Research Center, Shahid Beheshti University of Medical Sciences
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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