3-14145293-G-C

Variant names:

• chr3-14145293-G-C
• rs1015682387
• NM_004628.5:c.*648C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004628.5(XPC):​c.*648C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000367 in 545,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: XPC NM_004628.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 0 publications found

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]

ENSG00000268279 (HGNC:):

XPC-AS1 (HGNC:55014): (XPC antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPC	NM_004628.5	c.*648C>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12	c.*648C>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_004628.5	ENSP00000285021.8
ENSG00000268279	ENST00000608606.1	n.236-29G>C		intron_variant	Intron 3 of 4	5		ENSP00000476275.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000156 AC: 2 AN: 128552 AF XY: 0.0000285

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000966

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000367 AC: 2 AN: 545466 Hom.: 0 Cov.: 0 AF XY: 0.00000677 AC XY: 2 AN XY: 295370

African (AFR) AF: 0.00 AC: 0 AN: 15514

American (AMR) AF: 0.00 AC: 0 AN: 34212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19906

East Asian (EAS) AF: 0.0000312 AC: 1 AN: 32080

South Asian (SAS) AF: 0.0000161 AC: 1 AN: 62182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2422

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 315672

Other (OTH) AF: 0.00 AC: 0 AN: 30326

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.39
DANN	Benign	0.60
PhyloP100		-0.75

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

Other links and lift over

dbSNP: rs1015682387; hg19: chr3-14186793;