NM_000380.4(XPA):c.631C>T (p.Arg211Ter) AND Xeroderma pigmentosum

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 2018
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:: RCV000781923.1

Allele description [Variation Report for NM_000380.4(XPA):c.631C>T (p.Arg211Ter)]

NM_000380.4(XPA):c.631C>T (p.Arg211Ter)

Gene:

XPA:XPA, DNA damage recognition and repair factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.33

Genomic location:

Preferred name:

NM_000380.4(XPA):c.631C>T (p.Arg211Ter)

HGVS:

NC_000009.12:g.97684965G>A
NG_011642.1:g.17445C>T
NM_000380.4:c.631C>TMANE SELECT
NM_001354975.2:c.505C>T
NP_000371.1:p.Arg211Ter
NP_000371.1:p.Arg211Ter
NP_001341904.1:p.Arg169Ter
LRG_471t1:c.631C>T
LRG_471:g.17445C>T
LRG_471p1:p.Arg211Ter
NC_000009.11:g.100447247G>A
NM_000380.3:c.631C>T
NR_027302.2:n.679C>T
NR_149091.2:n.407C>T
NR_149092.2:n.573C>T
NR_149093.2:n.679C>T
NR_149094.2:n.573C>T

Protein change:

R169*

Links:

dbSNP: rs149226993

NCBI 1000 Genomes Browser:

rs149226993

Molecular consequence:

NR_027302.2:n.679C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149091.2:n.407C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149092.2:n.573C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149093.2:n.679C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149094.2:n.573C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000380.4:c.631C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354975.2:c.505C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000920349	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Nov 29, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27607234, 1372103 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000920349

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Nov 29, 2018)

germline

clinical testing

PubMed (2)
[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

Clinical and molecular epidemiological study of xeroderma pigmentosum in China: A case series of 19 patients.

Zhou EY, Wang H, Lin Z, Xu G, Ma Z, Zhao J, Feng C, Duo L, Yin J, Yang Y.

J Dermatol. 2017 Jan;44(1):71-75. doi: 10.1111/1346-8138.13576. Epub 2016 Sep 8.

PubMed [citation]

PMID:: 27607234

Identification of splicing mutations of the last nucleotides of exons, a nonsense mutation, and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum.

Satokata I, Tanaka K, Yuba S, Okada Y.

Mutat Res. 1992 Mar;273(2):203-12.

PubMed [citation]

PMID:: 1372103

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000920349.1

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

Description

Variant summary: XPA c.631C>T (p.Arg211X) 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. The variant allele was found at a frequency of 4.1e-06 in 245906 control chromosomes (gnomAD). c.631C>T has been reported in the literature in multiple homozygote and compound heterozygote individuals affected with Xeroderma Pigmentosum (Satokata_1992, Zhou_2017). These data indicate that the variant is very likely to be associated with disease. A functional study indicates that the variant would "cause instability of the XPAC mRNA and loss of repair activity of the XPAC protein." (Satokata_1992) A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cties the variant as likely pathogenic. 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: Jun 29, 2025

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