rs3731125

chr3-14159852-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004628.5(XPC):c.901-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 1,542,596 control chromosomes in the GnomAD database, including 4,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (500 hom., cov: 32)
  • Exomes 𝑓: 0.077 (4401 hom.)
• Consequence: XPC NM_004628.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.94

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-14159852-T-C is Benign according to our data. Variant chr3-14159852-T-C is described in ClinVar as [Benign]. Clinvar id is 259475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPC	NM_004628.5	c.901-22A>G		intron_variant		ENST00000285021.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPC	ENST00000285021.12	c.901-22A>G		intron_variant		1	NM_004628.5	P1
XPC-AS1	ENST00000627116.2	n.457-6024T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0769 AC: 11695 AN: 152044 Hom.: 496 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.0665

GnomAD3 exomes AF: 0.0741 AC: 11673 AN: 157614 Hom.: 499 AF XY: 0.0780 AC XY: 6487 AN XY: 83188

Gnomad AFR exome AF: 0.0761

Gnomad AMR exome AF: 0.0328

Gnomad ASJ exome AF: 0.0776

Gnomad EAS exome AF: 0.0130

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0803

Gnomad OTH exome AF: 0.0657

GnomAD4 exome AF: 0.0768 AC: 106733 AN: 1390434 Hom.: 4401 Cov.: 27 AF XY: 0.0778 AC XY: 53379 AN XY: 686502

Gnomad4 AFR exome AF: 0.0751

Gnomad4 AMR exome AF: 0.0348

Gnomad4 ASJ exome AF: 0.0781

Gnomad4 EAS exome AF: 0.0190

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0767

Gnomad4 OTH exome AF: 0.0725

GnomAD4 genome AF: 0.0770 AC: 11715 AN: 152162 Hom.: 500 Cov.: 32 AF XY: 0.0775 AC XY: 5762 AN XY: 74378

Gnomad4 AFR AF: 0.0773

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0821

Gnomad4 OTH AF: 0.0715

Alfa AF: 0.0755 Hom.: 466

Bravo AF: 0.0698

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Xeroderma pigmentosum group A Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Xeroderma pigmentosum, group C Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.0020
Dann	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3731125; hg19: chr3-14201352; COSMIC: COSV53203469; COSMIC: COSV53203469;