chr3-14152930-T-G

Position:

• chr3-14152930-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004628.5(XPC):​c.2034-514A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 152,408 control chromosomes in the GnomAD database, including 421 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 0.069 (421 hom., cov: 33)
  • Exomes 𝑓: 0.064 (0 hom.)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPC	NM_004628.5	c.2034-514A>C		intron_variant		ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12	c.2034-514A>C		intron_variant		1	NM_004628.5	ENSP00000285021.8

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10546 AN: 152150 Hom.: 418 Cov.: 33

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0473

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0643 AC: 9 AN: 140 Hom.: 0 Cov.: 0 AF XY: 0.0294 AC XY: 2 AN XY: 68

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0833

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0694 AC: 10562 AN: 152268 Hom.: 421 Cov.: 33 AF XY: 0.0698 AC XY: 5197 AN XY: 74444

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0822 Hom.: 73

Bravo AF: 0.0612

Asia WGS AF: 0.0720 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.047
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs9653966; hg19: chr3-14194430;