NM_004628.5(XPC):c.2251-1G>C AND Xeroderma pigmentosum, group C

Germline classification:: Pathogenic (9 submissions)
Last evaluated:: Mar 21, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000170434.21

Allele description [Variation Report for NM_004628.5(XPC):c.2251-1G>C]

NM_004628.5(XPC):c.2251-1G>C

Gene:

XPC:XPC complex subunit, DNA damage recognition and repair factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_004628.5(XPC):c.2251-1G>C

HGVS:

NC_000003.12:g.14148732C>G
NG_011763.1:g.34941G>C
NG_098743.1:g.280C>G
NM_001354726.2:c.1672-1G>C
NM_001354727.2:c.2245-1G>C
NM_001354729.2:c.2233-1G>C
NM_001354730.2:c.2005-1G>C
NM_004628.5:c.2251-1G>CMANE SELECT
LRG_472t1:c.2251-1G>C
LRG_472:g.34941G>C
NC_000003.11:g.14190232C>G
NM_004628.4:c.2251-1G>C

Links:

dbSNP: rs754673606

NCBI 1000 Genomes Browser:

rs754673606

Molecular consequence:

NM_001354726.2:c.1672-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354727.2:c.2245-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354729.2:c.2233-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354730.2:c.2005-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004628.5:c.2251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

Condition(s)

Name:: Xeroderma pigmentosum, group C (XPC)
Synonyms:: XERODERMA PIGMENTOSUM III; XP, GROUP C; Xeroderma pigmentosum, complementation group C
Identifiers:: MONDO: MONDO:0010211; MedGen: C2752147; Orphanet: 910; OMIM: 278720

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222871	Claritas Genomics	criteria provided, single submitter (ACMG Guidelines, 2007)	Pathogenic (Oct 17, 2007)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000893637	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001335286	Medical Molecular Genetics Department, National Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 1, 2015)	germline	research	PubMed (2) [See all records that cite these PMIDs] 21482201, 25741868
SCV001652707	DNA Repair Laboratory, Institute of Biomedical Sciences - University of Sao Paulo	criteria provided, single submitter (DNA Repair Laboratory Assertion Criteria)	Pathogenic (Mar 1, 2021)	germline	research	PubMed (6) [See all records that cite these PMIDs] 21482201, 32239545, 29569758, 31017654, 26884178, 35111200 Citation Link,
SCV002060371	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Pathogenic (Nov 19, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV003807449	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 31, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004206963	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 21, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004805136	Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 17, 2024)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV005061737	Dr.Nikuei Genetic Center	no assertion criteria provided	Pathogenic	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	7	not provided	not provided	2	yes	clinical testing, research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Europen, African, Native	germline	yes	1	not provided	not provided	not provided	not provided	research

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee.

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients.

Santiago KM, Castro LP, Neto JPD, de Nóbrega AF, Pinto CAL, Ashton-Prolla P, Pinto E Vairo F, de Medeiros PFV, Ribeiro EM, Ribeiro BFR, do Valle FF, Doriqui MJR, Leite CHB, Rocha RM, Moura LMS, Munford V, Galante PAF, Menck CFM, Rogatto SR, Achatz MI.

J Eur Acad Dermatol Venereol. 2020 Oct;34(10):2392-2401. doi: 10.1111/jdv.16405. Epub 2020 May 21.

PubMed [citation]

PMID:: 32239545

See all PubMed Citations (8)

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Claritas Genomics, SCV000222871.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV000893637.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Medical Molecular Genetics Department, National Research Center, SCV001335286.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	yes	research	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		4	not provided	not provided	not provided

From DNA Repair Laboratory, Institute of Biomedical Sciences - University of Sao Paulo, SCV001652707.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Europen, African, Native	1	not provided	not provided	research	PubMed (6)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV002060371.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

NM_004628.4(XPC):c.2251-1G>C is a canonical splice variant classified as pathogenic in the context of xeroderma pigmentosum group C. c.2251-1G>C has been observed in cases with relevant disease (PMID: 21482201). Functional assessments of this variant are not available in the literature. c.2251-1G>C has been observed in population frequency databases (gnomAD: AFR 0.04%). In summary, NM_004628.4(XPC):c.2251-1G>C is a canonical splice variant in a gene where loss of function is a known mechanism of disease, is predicted to disrupt protein function, and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV003807449.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)
2	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 strong, PM2 moderated, PM3 strong, PP1 supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Baylor Genetics, SCV004206963.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre, SCV004805136.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Dr.Nikuei Genetic Center, SCV005061737.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 25, 2025

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