chr3-14145845-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

35 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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	ENST00000285021.12 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

GnomAD2 exomes

AF:

0.249

AC:

48463

AN:

194356

AF XY:

0.249

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 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

African (AFR)

AF:

0.108

AC:

3224

AN:

29760

American (AMR)

AF:

0.227

AC:

8609

AN:

37856

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

4965

AN:

22818

East Asian (EAS)

AF:

0.377

AC:

14395

AN:

38222

South Asian (SAS)

AF:

0.207

AC:

16047

AN:

77480

European-Finnish (FIN)

AF:

0.344

AC:

16394

AN:

47616

Middle Eastern (MID)

AF:

0.195

AC:

744

AN:

3810

European-Non Finnish (NFE)

AF:

0.254

AC:

253385

AN:

996716

Other (OTH)

AF:

0.247

AC:

13502

AN:

54566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

12295

24590

36884

49179

61474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.227

AC:

34462

AN:

152056

Hom.:

4412

Cov.:

AF XY:

0.231

AC XY:

17188

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.117

AC:

4866

AN:

41506

American (AMR)

AF:

0.247

AC:

3780

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

773

AN:

3470

East Asian (EAS)

AF:

0.397

AC:

2039

AN:

5130

South Asian (SAS)

AF:

0.213

AC:

1026

AN:

4816

European-Finnish (FIN)

AF:

0.364

AC:

3848

AN:

10584

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.252

AC:

17130

AN:

67936

Other (OTH)

AF:

0.257

AC:

542

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1311

2622

3933

5244

6555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Dec 05, 2021

Genome-Nilou Lab

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. -

Apr 26, 2017

Counsyl

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 07, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

DANN

Benign

0.44

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr3-14145845-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over