chr3-14145257-C-G
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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
NM_004628.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0480
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 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 |
---|---|---|---|---|---|---|---|
XPC | NM_004628.5 | c.*684G>C | 3_prime_UTR_variant | 16/16 | ENST00000285021.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPC | ENST00000285021.12 | c.*684G>C | 3_prime_UTR_variant | 16/16 | 1 | NM_004628.5 | P1 | ||
XPC-AS1 | ENST00000420253.3 | n.460-65C>G | intron_variant, non_coding_transcript_variant | 4 | |||||
XPC-AS1 | ENST00000428681.3 | n.374-65C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.882 AC: 134115AN: 152134Hom.: 59223 Cov.: 33
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GnomAD3 exomes AF: 0.904 AC: 109766AN: 121382Hom.: 49803 AF XY: 0.902 AC XY: 59493AN XY: 65926
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GnomAD4 exome AF: 0.887 AC: 473977AN: 534196Hom.: 210734 Cov.: 0 AF XY: 0.888 AC XY: 256281AN XY: 288562
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GnomAD4 genome AF: 0.882 AC: 134230AN: 152252Hom.: 59278 Cov.: 33 AF XY: 0.886 AC XY: 65973AN XY: 74436
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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 submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Arrhythmogenic right ventricular cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Xeroderma pigmentosum, group C Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at