chr3-14158778-CTT-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004628.5(XPC):c.1103_1104delAA(p.Gln368ArgfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,818 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
XPC
NM_004628.5 frameshift
NM_004628.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.169
Publications
3 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: Pathogenic. The variant received 18 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 3-14158778-CTT-C is Pathogenic according to our data. Variant chr3-14158778-CTT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 267279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.1103_1104delAA | p.Gln368ArgfsTer6 | frameshift | Exon 9 of 16 | NP_004619.3 | |||
| XPC | c.1103_1104delAA | p.Gln368ArgfsTer6 | frameshift | Exon 9 of 16 | NP_001341656.1 | A0ABB0MVJ4 | |||
| XPC | c.1085_1086delAA | p.Gln362ArgfsTer6 | 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.1103_1104delAA | p.Gln368ArgfsTer6 | frameshift | Exon 9 of 16 | ENSP00000285021.8 | Q01831-1 | ||
| XPC | TSL:1 | n.*556_*557delAA | non_coding_transcript_exon | Exon 8 of 15 | ENSP00000424548.1 | Q01831-3 | |||
| XPC | TSL:1 | n.*556_*557delAA | 3_prime_UTR | Exon 8 of 15 | ENSP00000424548.1 | Q01831-3 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152116
Hom.:
Cov.:
32
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:
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461702Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727134 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1461702
Hom.:
AF XY:
AC XY:
3
AN XY:
727134
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
1
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:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
5
AN:
1111868
Other (OTH)
AF:
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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55-60
60-65
65-70
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>80
Age
GnomAD4 genome 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152116
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74318
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41416
American (AMR)
AF:
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5168
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
3
AN:
68020
Other (OTH)
AF:
AC:
0
AN:
2088
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
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
5
-
-
Xeroderma pigmentosum, group C (5)
1
-
-
Familial prostate cancer (1)
1
-
-
not provided (1)
1
-
-
Xeroderma pigmentosum (1)
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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