chr13-102873304-ATC-A
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_000123.4(ERCC5):c.2929_2930delCT(p.Leu977ValfsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ERCC5
NM_000123.4 frameshift
NM_000123.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.70
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: Likely_pathogenic. The variant received 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 13-102873304-ATC-A is Pathogenic according to our data. Variant chr13-102873304-ATC-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 373982.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.2929_2930delCT | p.Leu977ValfsTer17 | frameshift_variant | Exon 14 of 15 | ENST00000652225.2 | NP_000114.3 | |
| BIVM-ERCC5 | NM_001204425.2 | c.4291_4292delCT | p.Leu1431ValfsTer17 | frameshift_variant | Exon 22 of 23 | NP_001191354.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ERCC5 | ENST00000652225.2 | c.2929_2930delCT | p.Leu977ValfsTer17 | frameshift_variant | Exon 14 of 15 | NM_000123.4 | ENSP00000498881.2 | |||
| BIVM-ERCC5 | ENST00000639435.1 | c.4291_4292delCT | p.Leu1431ValfsTer17 | frameshift_variant | Exon 24 of 25 | 5 | ENSP00000491742.1 | |||
| BIVM-ERCC5 | ENST00000639132.1 | c.3604_3605delCT | p.Leu1202ValfsTer17 | frameshift_variant | Exon 23 of 24 | 5 | ENSP00000492684.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461828Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727218 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461828
Hom.:
AF XY:
AC XY:
0
AN XY:
727218
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39678
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111982
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
1
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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4
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<30
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dysarthria;C0037772:Spastic paraplegia;C0152025:Polyneuropathy;C0338656:Cognitive impairment;C0728829:Pes cavus;C0740279:Cerebellar atrophy;C1842581:Abnormal corpus callosum morphology;C2051831:Pectus excavatum Pathogenic:1
Jun 15, 2015
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Significance:Likely 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
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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