3-14169601-A-G

Position:

• chr3-14169601-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.412+837T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,160 control chromosomes in the GnomAD database, including 7,155 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 0.29 (7155 hom., cov: 32)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPC	NM_004628.5	c.412+837T>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.412+837T>C		intron_variant		1	NM_004628.5	ENSP00000285021.8

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44377 AN: 152042 Hom.: 7154 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44405 AN: 152160 Hom.: 7155 Cov.: 32 AF XY: 0.297 AC XY: 22115 AN XY: 74384

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.315

Alfa AF: 0.307 Hom.: 9904

Bravo AF: 0.272

Asia WGS AF: 0.310 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.31

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: rs2733537; hg19: chr3-14211101;