NM_004628.5(XPC):c.1704T>A (p.Tyr568Ter) AND Xeroderma pigmentosum

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 25, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001192698.1

Allele description [Variation Report for NM_004628.5(XPC):c.1704T>A (p.Tyr568Ter)]

NM_004628.5(XPC):c.1704T>A (p.Tyr568Ter)

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.1704T>A (p.Tyr568Ter)

HGVS:

NC_000003.12:g.14158179A>T
NG_011763.1:g.25494T>A
NM_001354726.2:c.1125T>A
NM_001354727.2:c.1704T>A
NM_001354729.2:c.1686T>A
NM_001354730.2:c.1626+78T>A
NM_004628.5:c.1704T>AMANE SELECT
NP_001341655.1:p.Tyr375Ter
NP_001341656.1:p.Tyr568Ter
NP_001341658.1:p.Tyr562Ter
NP_004619.3:p.Tyr568Ter
LRG_472t1:c.1704T>A
LRG_472:g.25494T>A
NC_000003.11:g.14199679A>T
NC_000003.11:g.14199679A>T
NM_004628.4:c.1704T>A
NR_148950.2:n.1737T>A
NR_148951.2:n.1613T>A

Protein change:

Y375*

Links:

dbSNP: rs1695999145

NCBI 1000 Genomes Browser:

rs1695999145

Molecular consequence:

NM_001354730.2:c.1626+78T>A - intron variant - [Sequence Ontology: SO:0001627]
NR_148950.2:n.1737T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148951.2:n.1613T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001354726.2:c.1125T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354727.2:c.1704T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354729.2:c.1686T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_004628.5:c.1704T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Xeroderma pigmentosum (XP)
Synonyms:: Xeroderma pigmentosa
Identifiers:: MONDO: MONDO:0019600; MedGen: C0043346

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Golgi membrane protein 1 [Mus musculus]
Golgi membrane protein 1 [Mus musculus]
gi|78190502|ref|NP_081583.3|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001360988	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Nov 25, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20054342, 28615033, 23278166 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001360988

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Nov 25, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A prevalent mutation with founder effect in xeroderma pigmentosum group C from north Africa.

Soufir N, Ged C, Bourillon A, Austerlitz F, Chemin C, Stary A, Armier J, Pham D, Khadir K, Roume J, Hadj-Rabia S, Bouadjar B, Taieb A, de Verneuil H, Benchiki H, Grandchamp B, Sarasin A.

J Invest Dermatol. 2010 Jun;130(6):1537-42. doi: 10.1038/jid.2009.409. Epub 2010 Jan 7.

PubMed [citation]

PMID:: 20054342

A novel frameshift mutation in the XPC gene in a Moroccan patient: a case report.

Doubaj Y, Smaili W, Laarabi FZ, Sefiani A.

J Med Case Rep. 2017 Jun 15;11(1):158. doi: 10.1186/s13256-017-1311-6.

PubMed [citation]

PMID:: 28615033
PMCID:: PMC5471900

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360988.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: XPC c.1704T>A (p.Tyr568X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249336 control chromosomes. c.1704T>A has been reported in the literature in individuals affected with Xeroderma pigmentosum (example, Doubaj_2017, Hadj-Rabia_2013, Soufir_2010). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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

Last Updated: Sep 29, 2024

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