rs201273381

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_004628.5(XPC):c.37G>C(p.Gly13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000924 in 1,612,958 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 1 hom. )

Consequence

XPC
NM_004628.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:6O:1

Conservation

PhyloP100: 0.00900

Publications

5 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 Gene-Disease associations (from GenCC):

xeroderma pigmentosum group C
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Genomics England PanelApp, ClinGen, G2P
xeroderma pigmentosum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

XPC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022016793).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000499 (76/152392) while in subpopulation NFE AF = 0.00101 (69/68038). AF 95% confidence interval is 0.000821. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004628.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XPC	NM_004628.5	MANE Select	c.37G>C	p.Gly13Arg	missense	Exon 1 of 16	NP_004619.3
XPC	NM_001354727.2		c.37G>C	p.Gly13Arg	missense	Exon 1 of 16	NP_001341656.1	A0ABB0MVJ4
XPC	NM_001354729.2		c.37G>C	p.Gly13Arg	missense	Exon 1 of 16	NP_001341658.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XPC	ENST00000285021.12	TSL:1 MANE Select	c.37G>C	p.Gly13Arg	missense	Exon 1 of 16	ENSP00000285021.8	Q01831-1
XPC	ENST00000476581.6	TSL:1	n.37G>C		non_coding_transcript_exon	Exon 1 of 15	ENSP00000424548.1	Q01831-3
XPC	ENST00000850575.1		c.37G>C	p.Gly13Arg	missense	Exon 1 of 16	ENSP00000520865.1	A0ABB0MVJ4

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000346

AC:

AN:

245612

AF XY:

0.000343

show subpopulations

Gnomad AFR exome

AF:

0.000135

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000721

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000968

AC:

1414

AN:

1460566

Hom.:

Cov.:

AF XY:

0.000879

AC XY:

639

AN XY:

726646

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33450

American (AMR)

AF:

0.0000224

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00116

AC:

1294

AN:

1111578

Other (OTH)

AF:

0.00182

AC:

110

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

182

274

365

456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.000499

AC:

AN:

152392

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41598

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000772

Hom.:

Bravo

AF:

0.000468

ESP6500AA

AF:

0.000258

AC:

ESP6500EA

AF:

0.000608

AC:

ExAC

AF:

0.000307

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Xeroderma pigmentosum, group C (3)

not provided (2)

Xeroderma pigmentosum (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.2

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.54

M_CAP

Benign

0.029

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PhyloP100

0.0090

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.66

REVEL

Benign

0.052

Sift

Uncertain

0.0060

Sift4G

Benign

0.19

Polyphen

0.0010

Vest4

0.16

MutPred

0.22

Gain of glycosylation at S18 (P = 4e-04)

MVP

0.17

MPC

0.14

ClinPred

0.035

GERP RS

0.79

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.048

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over