rs1280251289
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_004628.5(XPC):c.2703delT(p.Ala902ProfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
XPC
NM_004628.5 frameshift
NM_004628.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.189
Publications
0 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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0425 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| XPC | ENST00000285021.12 | c.2703delT | p.Ala902ProfsTer15 | frameshift_variant | Exon 16 of 16 | 1 | NM_004628.5 | ENSP00000285021.8 | ||
| ENSG00000268279 | ENST00000608606.1 | n.*198+378delA | intron_variant | Intron 4 of 4 | 5 | ENSP00000476275.1 |
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151672Hom.: 0 Cov.: 28 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151672
Hom.:
Cov.:
28
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000402 AC: 1AN: 248808 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
248808
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461162Hom.: 0 Cov.: 37 AF XY: 0.00000550 AC XY: 4AN XY: 726850 show subpopulations
GnomAD4 exome
AF:
AC:
9
AN:
1461162
Hom.:
Cov.:
37
AF XY:
AC XY:
4
AN XY:
726850
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
1
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86198
European-Finnish (FIN)
AF:
AC:
0
AN:
53126
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
8
AN:
1111674
Other (OTH)
AF:
AC:
0
AN:
60362
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000659 AC: 1AN: 151672Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1AN XY: 74054 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151672
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
74054
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41238
American (AMR)
AF:
AC:
0
AN:
15234
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5146
South Asian (SAS)
AF:
AC:
0
AN:
4764
European-Finnish (FIN)
AF:
AC:
0
AN:
10588
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67922
Other (OTH)
AF:
AC:
0
AN:
2080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Xeroderma pigmentosum, group C Uncertain:1
Feb 28, 2018
Counsyl
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:clinical testing
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -
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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