VCV000940041.10 - ClinVar

NM_004628.5(XPC):c.1290_1295del (p.Tyr430_Glu432delinsTer)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (2)

2 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004628.5(XPC):c.1290_1295del (p.Tyr430_Glu432delinsTer)

Variation ID: 940041 Accession: VCV000940041.10

Type and length

Deletion, 6 bp

Location

Cytogenetic: 3p25.1 3: 14158588-14158593 (GRCh38) [ NCBI UCSC ] 3: 14200088-14200093 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 16, 2020	Feb 15, 2026	May 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_004628.5:c.1290_1295del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004619.3:p.Tyr430_Glu432delinsTer	nonsense
NM_001354726.2:c.711_716del	NP_001341655.1:p.Tyr237_Glu239delinsTer	nonsense
NM_001354727.2:c.1290_1295del	NP_001341656.1:p.Tyr430_Glu432delinsTer	nonsense
NM_001354729.2:c.1272_1277del	NP_001341658.1:p.Tyr424_Glu426delinsTer	nonsense
NM_001354730.2:c.1290_1295del	NP_001341659.1:p.Tyr430_Glu432delinsTer	nonsense
NR_148950.2:n.1323_1328del		non-coding transcript variant
NR_148951.2:n.1199_1204del		non-coding transcript variant
NC_000003.12:g.14158589_14158594del
NC_000003.11:g.14200089_14200094del
NG_011763.1:g.25080_25085del
LRG_472:g.25080_25085del
LRG_472t1:c.1290_1295del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000003.12:14158587:TCTTTAT:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA899798109 dbSNP: rs1448891857 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
XPC		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	1104	1203

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Pathogenic (1)	criteria provided, single submitter	Mar 18, 2023	RCV001209544.10
Xeroderma pigmentosum, group C	Pathogenic (1)	criteria provided, single submitter	May 1, 2024	RCV005029763.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 01, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Xeroderma pigmentosum, group C	Fulgent Genetics, Fulgent Genetics Accession: SCV005656580.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Mar 18, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001380984.7 First in ClinVar: Jul 16, 2020 Last updated: Feb 15, 2026	Publications: PubMed (3) PubMed: 16081512‚ 23173980‚ 25256075 Comment: show This sequence change creates a premature translational stop signal (p.Tyr430*) in the XPC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in XPC are known to be pathogenic (PMID: 23173980, 25256075). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 16081512). ClinVar contains an entry for this variant (Variation ID: 940041). For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change creates a premature translational stop signal (p.Tyr430*) in the XPC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in XPC are known to be pathogenic (PMID: 23173980, 25256075). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 16081512). ClinVar contains an entry for this variant (Variation ID: 940041). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Genotype-phenotype correlation of xeroderma pigmentosum in a Chinese Han population.	Sun Z	The British journal of dermatology	2015	PMID: 25256075
Molecular genetic analysis of 16 XP-C patients from Germany: environmental factors predominately contribute to phenotype variations.	Schäfer A	Experimental dermatology	2013	PMID: 23173980
Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients.	Khan SG	Carcinogenesis	2006	PMID: 16081512

Text-mined citations for rs1448891857 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026