rs13099160

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004628.5(XPC):​c.901-1469T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 152,278 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.040 ( 178 hom., cov: 32)

Consequence

XPC
NM_004628.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.288
Variant links:
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]
XPC-AS1 (HGNC:55014): (XPC antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
XPCNM_004628.5 linkuse as main transcriptc.901-1469T>C intron_variant ENST00000285021.12 NP_004619.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
XPCENST00000285021.12 linkuse as main transcriptc.901-1469T>C intron_variant 1 NM_004628.5 ENSP00000285021 P1Q01831-1
XPCENST00000476581.6 linkuse as main transcriptc.*354-1469T>C intron_variant, NMD_transcript_variant 1 ENSP00000424548 Q01831-3
XPC-AS1ENST00000627116.2 linkuse as main transcriptn.457-4577A>G intron_variant, non_coding_transcript_variant 5
XPCENST00000477324.6 linkuse as main transcriptn.379-1469T>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0405
AC:
6168
AN:
152160
Hom.:
178
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00994
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0312
Gnomad ASJ
AF:
0.0450
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00954
Gnomad FIN
AF:
0.0614
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0638
Gnomad OTH
AF:
0.0383
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0405
AC:
6166
AN:
152278
Hom.:
178
Cov.:
32
AF XY:
0.0391
AC XY:
2913
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00991
Gnomad4 AMR
AF:
0.0311
Gnomad4 ASJ
AF:
0.0450
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00934
Gnomad4 FIN
AF:
0.0614
Gnomad4 NFE
AF:
0.0638
Gnomad4 OTH
AF:
0.0379
Alfa
AF:
0.0599
Hom.:
43
Bravo
AF:
0.0357
Asia WGS
AF:
0.00433
AC:
15
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.8
DANN
Benign
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13099160; hg19: chr3-14202799; API