rs3731124

Variant names:

• chr3-14159900-T-C
• rs3731124
• NM_004628.5:c.901-70A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-14159900-T-C
• chr3-14159900-T-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.901-70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,291,654 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: 0.0000023 (0 hom.)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• 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]

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.901-70A>G		intron_variant	Intron 7 of 15	ENST00000285021.12	NP_004619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12	c.901-70A>G		intron_variant	Intron 7 of 15	1	NM_004628.5	ENSP00000285021.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000232 AC: 3 AN: 1291654 Hom.: 0 Cov.: 19 AF XY: 0.00000312 AC XY: 2 AN XY: 641848

African (AFR) AF: 0.00 AC: 0 AN: 29310

American (AMR) AF: 0.00 AC: 0 AN: 35264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24504

East Asian (EAS) AF: 0.00 AC: 0 AN: 35092

South Asian (SAS) AF: 0.00 AC: 0 AN: 76664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5108

European-Non Finnish (NFE) AF: 0.00000305 AC: 3 AN: 984456

Other (OTH) AF: 0.00 AC: 0 AN: 54500

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	4.8
DANN	Benign	0.49
PhyloP100		0.17

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: rs3731124; hg19: chr3-14201400;