3-14145845-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004628.5(XPC):c.*96C>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 0.25 in 1,460,900 control chromosomes in the GnomAD database, including 47,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4412 hom., cov: 32)

Exomes 𝑓: 0.25 ( 43427 hom. )

Consequence

XPC
NM_004628.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.21

Variant links:

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 links:

ENSG00000268279 (HGNC:):

ENSG00000268279 links:

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

XPC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-14145845-G-C is Benign according to our data. Variant chr3-14145845-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 343560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPC	NM_004628.5 link	c.*96C>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000285021.12	NP_004619.3	Q01831-1X5DRB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021 link	c.*96C>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_004628.5	ENSP00000285021.8		Q01831-1
ENSG00000268279	ENST00000608606.1 link	n.*198+162G>C		intron_variant	Intron 4 of 4	5		ENSP00000476275.1		V9GY05

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34451

AN:

151938

Hom.:

4415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.256

GnomAD3 exomes

AF:

0.249

AC:

48463

AN:

194356

Hom.:

6255

AF XY:

0.249

AC XY:

26166

AN XY:

105016

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.388

Gnomad SAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.253

AC:

331265

AN:

1308844

Hom.:

43427

Cov.:

AF XY:

0.252

AC XY:

163836

AN XY:

650832

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.227

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.377

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.227

AC:

34462

AN:

152056

Hom.:

4412

Cov.:

AF XY:

0.231

AC XY:

17188

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.247

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.213

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.141

Hom.:

403

Bravo

AF:

0.215

Asia WGS

AF:

0.261

AC:

905

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group C

Benign:3

Apr 26, 2017

Counsyl

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Xeroderma pigmentosum

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arrhythmogenic right ventricular cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

DANN

Benign

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over