chr3-14159852-T-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.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 (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.077 ( 500 hom., cov: 32)

Exomes 𝑓: 0.077 ( 4401 hom. )

Consequence

XPC
NM_004628.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.94

Publications

9 publications found

Variant links:

COSMIC-nc: COSV53203469

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:

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 VariationId 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 rank	MANE	Protein	UniProt
XPC	NM_004628.5 link	c.901-22A>G		intron_variant	Intron 7 of 15	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.901-22A>G		intron_variant	Intron 7 of 15	1	NM_004628.5	ENSP00000285021.8		Q01831-1

Frequencies

GnomAD3 genomes

AF:

0.0769

AC:

11695

AN:

152044

Hom.:

496

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0741

AC:

11673

AN:

157614

AF XY:

0.0780

show subpopulations

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 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.:

AF XY:

0.0778

AC XY:

53379

AN XY:

686502

show subpopulations

African (AFR)

AF:

0.0751

AC:

2357

AN:

31370

American (AMR)

AF:

0.0348

AC:

1241

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

1961

AN:

25112

East Asian (EAS)

AF:

0.0190

AC:

680

AN:

35706

South Asian (SAS)

AF:

0.111

AC:

8793

AN:

78998

European-Finnish (FIN)

AF:

0.103

AC:

5103

AN:

49312

Middle Eastern (MID)

AF:

0.0493

AC:

280

AN:

5682

European-Non Finnish (NFE)

AF:

0.0767

AC:

82132

AN:

1070824

Other (OTH)

AF:

0.0725

AC:

4186

AN:

57726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5201

10402

15604

20805

26006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3024

6048

9072

12096

15120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0770

AC:

11715

AN:

152162

Hom.:

500

Cov.:

AF XY:

0.0775

AC XY:

5762

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0773

AC:

3210

AN:

41504

American (AMR)

AF:

0.0503

AC:

769

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0769

AC:

267

AN:

3470

East Asian (EAS)

AF:

0.0118

AC:

AN:

5178

South Asian (SAS)

AF:

0.107

AC:

516

AN:

4814

European-Finnish (FIN)

AF:

0.105

AC:

1109

AN:

10582

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0821

AC:

5584

AN:

68012

Other (OTH)

AF:

0.0715

AC:

151

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

542

1085

1627

2170

2712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0748

Hom.:

592

Bravo

AF:

0.0698

Asia WGS

AF:

0.0740

AC:

259

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group C

Benign:2

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 02, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Xeroderma pigmentosum group A

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: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

-0.88

CADD

Benign

0.0020

(source)

DANN

Benign

0.26

PhyloP100

-1.9

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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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