rs13099160

chr3-14161299-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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)

ACMG classification

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	UniProt
XPC	NM_004628.5	c.901-1469T>C		intron_variant		ENST00000285021.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPC	ENST00000285021.12	c.901-1469T>C		intron_variant		1	NM_004628.5	P1
XPC	ENST00000476581.6	c.*354-1469T>C		intron_variant, NMD_transcript_variant		1
XPC-AS1	ENST00000627116.2	n.457-4577A>G		intron_variant, non_coding_transcript_variant		5
XPC	ENST00000477324.6	n.379-1469T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 6168 AN: 152160 Hom.: 178 Cov.: 32

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

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

Other links and lift over

dbSNP: rs13099160; hg19: chr3-14202799;