chr3-14145257-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004628.5(XPC):​c.*684G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 686,448 control chromosomes in the GnomAD database, including 270,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59278 hom., cov: 33)
Exomes 𝑓: 0.89 ( 210734 hom. )

Consequence

XPC
NM_004628.5 3_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.0480
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 3-14145257-C-G is Benign according to our data. Variant chr3-14145257-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 343550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XPCNM_004628.5 linkuse as main transcriptc.*684G>C 3_prime_UTR_variant 16/16 ENST00000285021.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XPCENST00000285021.12 linkuse as main transcriptc.*684G>C 3_prime_UTR_variant 16/161 NM_004628.5 P1Q01831-1
XPC-AS1ENST00000420253.3 linkuse as main transcriptn.460-65C>G intron_variant, non_coding_transcript_variant 4
XPC-AS1ENST00000428681.3 linkuse as main transcriptn.374-65C>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.882
AC:
134115
AN:
152134
Hom.:
59223
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.872
Gnomad AMI
AF:
0.921
Gnomad AMR
AF:
0.924
Gnomad ASJ
AF:
0.883
Gnomad EAS
AF:
0.997
Gnomad SAS
AF:
0.928
Gnomad FIN
AF:
0.909
Gnomad MID
AF:
0.873
Gnomad NFE
AF:
0.861
Gnomad OTH
AF:
0.888
GnomAD3 exomes
AF:
0.904
AC:
109766
AN:
121382
Hom.:
49803
AF XY:
0.902
AC XY:
59493
AN XY:
65926
show subpopulations
Gnomad AFR exome
AF:
0.876
Gnomad AMR exome
AF:
0.940
Gnomad ASJ exome
AF:
0.877
Gnomad EAS exome
AF:
0.999
Gnomad SAS exome
AF:
0.920
Gnomad FIN exome
AF:
0.910
Gnomad NFE exome
AF:
0.866
Gnomad OTH exome
AF:
0.890
GnomAD4 exome
AF:
0.887
AC:
473977
AN:
534196
Hom.:
210734
Cov.:
0
AF XY:
0.888
AC XY:
256281
AN XY:
288562
show subpopulations
Gnomad4 AFR exome
AF:
0.871
Gnomad4 AMR exome
AF:
0.936
Gnomad4 ASJ exome
AF:
0.879
Gnomad4 EAS exome
AF:
0.991
Gnomad4 SAS exome
AF:
0.923
Gnomad4 FIN exome
AF:
0.907
Gnomad4 NFE exome
AF:
0.864
Gnomad4 OTH exome
AF:
0.886
GnomAD4 genome
AF:
0.882
AC:
134230
AN:
152252
Hom.:
59278
Cov.:
33
AF XY:
0.886
AC XY:
65973
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.872
Gnomad4 AMR
AF:
0.924
Gnomad4 ASJ
AF:
0.883
Gnomad4 EAS
AF:
0.997
Gnomad4 SAS
AF:
0.929
Gnomad4 FIN
AF:
0.909
Gnomad4 NFE
AF:
0.861
Gnomad4 OTH
AF:
0.889
Alfa
AF:
0.859
Hom.:
6169
Bravo
AF:
0.885
Asia WGS
AF:
0.958
AC:
3331
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Xeroderma pigmentosum Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Arrhythmogenic right ventricular cardiomyopathy Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Xeroderma pigmentosum, group C Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
6.0
DANN
Benign
0.56

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: rs1126547; hg19: chr3-14186757; API