Variant 3-14167125-G-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.621+44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,501,174 control chromosomes in the GnomAD database, including 65,015 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9512 hom., cov: 32)

Exomes 𝑓: 0.28 ( 55503 hom. )

Consequence

XPC
NM_004628.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.387

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 3-14167125-G-C is Benign according to our data. Variant chr3-14167125-G-C is described in ClinVar as [Benign]. Clinvar id is 259472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPC	NM_004628.5 linkuse as main transcript	c.621+44C>G		intron_variant		ENST00000285021.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPC	ENST00000285021.12 linkuse as main transcript	c.621+44C>G		intron_variant		1	NM_004628.5	P1	Q01831-1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51370

AN:

151922

Hom.:

9495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.320

GnomAD3 exomes

AF:

0.306

AC:

54818

AN:

179048

Hom.:

8830

AF XY:

0.296

AC XY:

28516

AN XY:

96320

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.266

Gnomad SAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.279

GnomAD4 exome

AF:

0.282

AC:

380053

AN:

1349134

Hom.:

55503

Cov.:

AF XY:

0.280

AC XY:

186011

AN XY:

663176

show subpopulations

Gnomad4 AFR exome

AF:

0.515

Gnomad4 AMR exome

AF:

0.438

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.252

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.272

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.338

AC:

51445

AN:

152040

Hom.:

9512

Cov.:

AF XY:

0.339

AC XY:

25158

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.499

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.291

Hom.:

1327

Bravo

AF:

0.358

Asia WGS

AF:

0.342

AC:

1186

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

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

-0.98

CADD

Benign

0.39

DANN

Benign

0.40

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