rs794729654
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004628.5(XPC):c.1292_1293delAA(p.Lys431ArgfsTer6) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,548 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: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
XPC
NM_004628.5 frameshift
NM_004628.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.94
Publications
1 publications found
Genes affected
XPC (HGNC:12816): (XPC complex subunit, DNA damage recognition and repair factor) The protein encoded by this gene is a key component of the XPC complex, which plays an important role in the early steps of global genome nucleotide excision repair (NER). The encoded protein is important for damage sensing and DNA binding, and shows a preference for single-stranded DNA. Mutations in this gene or some other NER components can result in Xeroderma pigmentosum, a rare autosomal recessive disorder characterized by increased sensitivity to sunlight with the development of carcinomas at an early age. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
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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 3-14158589-CTT-C is Pathogenic according to our data. Variant chr3-14158589-CTT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 256.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004628.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| XPC | MANE Select | c.1292_1293delAA | p.Lys431ArgfsTer6 | frameshift | Exon 9 of 16 | NP_004619.3 | |||
| XPC | c.1292_1293delAA | p.Lys431ArgfsTer6 | frameshift | Exon 9 of 16 | NP_001341656.1 | A0ABB0MVJ4 | |||
| XPC | c.1274_1275delAA | p.Lys425ArgfsTer6 | frameshift | Exon 9 of 16 | NP_001341658.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| XPC | TSL:1 MANE Select | c.1292_1293delAA | p.Lys431ArgfsTer6 | frameshift | Exon 9 of 16 | ENSP00000285021.8 | Q01831-1 | ||
| XPC | TSL:1 | n.*745_*746delAA | non_coding_transcript_exon | Exon 8 of 15 | ENSP00000424548.1 | Q01831-3 | |||
| XPC | TSL:1 | n.*745_*746delAA | 3_prime_UTR | Exon 8 of 15 | ENSP00000424548.1 | Q01831-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461548Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727066 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461548
Hom.:
AF XY:
AC XY:
2
AN XY:
727066
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53254
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111866
Other (OTH)
AF:
AC:
0
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
3
-
-
Xeroderma pigmentosum, group C (3)
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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