Variant chr3-14159852-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: -1.94

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:

XPC-AS1 (HGNC:):

XPC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). 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	Protein	UniProt
XPC	NM_004628.5 linkuse as main transcript	c.901-22A>G		intron_variant		ENST00000285021.12	NP_004619.3	Q01831-1X5DRB1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPC	ENST00000285021.12 linkuse as main transcript	c.901-22A>G		intron_variant		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

GnomAD3 exomes

AF:

0.0741

AC:

11673

AN:

157614

Hom.:

499

AF XY:

0.0780

AC XY:

6487

AN XY:

83188

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 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.:

AF XY:

0.0778

AC XY:

53379

AN XY:

686502

show subpopulations

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.:

AF XY:

0.0775

AC XY:

5762

AN XY:

74378

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 02, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0020

DANN

Benign

0.26

BranchPoint Hunter

1.0

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

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