ClinVar Genomic variation as it relates to human health
NM_000380.4(XPA):c.349_353del (p.Leu117fs)
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.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000380.4(XPA):c.349_353del (p.Leu117fs)
Variation ID: 994 Accession: VCV000000994.12
- Type and length
-
Microsatellite, 5 bp
- Location
-
Cytogenetic: 9q22.33 9: 97689570-97689574 (GRCh38) [ NCBI UCSC ] 9: 100451852-100451856 (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 Apr 4, 2013 Feb 14, 2024 Dec 15, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000380.4:c.349_353del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000371.1:p.Leu117fs frameshift NM_000380.3:c.349_353del5 NM_000380.3:c.349_353delCTTAT NM_001354975.2:c.223_227del NP_001341904.1:p.Leu75fs frameshift NR_027302.2:n.392CTTAT[1] non-coding transcript variant NR_149093.2:n.392CTTAT[1] non-coding transcript variant NC_000009.12:g.97689571TAAGA[1] NC_000009.11:g.100451853TAAGA[1] NG_011642.1:g.12831CTTAT[1] LRG_471:g.12831CTTAT[1] - Protein change
- L117fs, L75fs
- Other names
- -
- Canonical SPDI
- NC_000009.12:97689569:ATAAGATAAGA:ATAAGA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe 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.
-
- Comment on variant
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 | ||
---|---|---|---|---|---|---|
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. |
|||
XPA | - | - |
GRCh38 GRCh37 |
354 | 399 |
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. |
---|---|---|---|---|
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Dec 15, 2023 | RCV000001049.6 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 11, 2018 | RCV000780797.1 | |
Pathogenic (1) |
criteria provided, single submitter
|
Nov 29, 2023 | RCV001057886.7 |
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. |
More information
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 11, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Xeroderma pigmentosum
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918359.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: XPA c.349_353delCTTAT (p.Leu117GlufsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: XPA c.349_353delCTTAT (p.Leu117GlufsX4) 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 7.2e-06 in 276628 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in XPA causing Xeroderma Pigmentosum (7.2e-06 vs 1.60e-03), allowing no conclusion about variant significance. The variant, c.349_353delCTTAT, has been reported in the literature in individuals affected with Xeroderma Pigmentosum (Ghafouri-Fard_2016, Christen-Zaech_2009, States_1998) where it was found to co-segregate with disease. These data indicate that the variant is likely to be associated with disease. At-least one study reports a hypersensitivity of patient derived fibroblasts to the killing effects of UV radiation, although quantitative data were not provided by the authors. 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. (less)
|
|
Pathogenic
(Dec 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Xeroderma pigmentosum group A
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003821872.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Sep 26, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Xeroderma pigmentosum group A
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000794422.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
|
|
Pathogenic
(Jul 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Xeroderma pigmentosum group A
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004206949.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Pathogenic
(Nov 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001222407.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Leu117Glufs*4) in the XPA gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Leu117Glufs*4) in the XPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in XPA are known to be pathogenic (PMID: 27607234). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 1339397, 19917958). ClinVar contains an entry for this variant (Variation ID: 994). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 01, 1992)
|
no assertion criteria provided
Method: literature only
|
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000021199.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In a cell line derived from a patient with XPA (278700), Satokata et al. (1992) found compound heterozygosity for 2 mutations in the XPA gene: … (more)
In a cell line derived from a patient with XPA (278700), Satokata et al. (1992) found compound heterozygosity for 2 mutations in the XPA gene: a 5-bp deletion causing a frameshift and premature termination, and C108F (611153.0002). (less)
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Clinical and molecular epidemiological study of xeroderma pigmentosum in China: A case series of 19 patients. | Zhou EY | The Journal of dermatology | 2017 | PMID: 27607234 |
A novel 5 nucleotide deletion in XPA gene is associated with severe neurological abnormalities. | Ghafouri-Fard S | Gene | 2016 | PMID: 26302748 |
Clinical profile and mutation analysis of xeroderma pigmentosum in Indian patients. | Tamhankar PM | Indian journal of dermatology, venereology and leprology | 2015 | PMID: 25566891 |
Unexpected occurrence of xeroderma pigmentosum in an uncle and nephew. | Christen-Zaech S | Archives of dermatology | 2009 | PMID: 19917958 |
Distribution of mutations in the human xeroderma pigmentosum group A gene and their relationships to the functional regions of the DNA damage recognition protein. | States JC | Human mutation | 1998 | PMID: 9671271 |
Molecular basis of group A xeroderma pigmentosum: a missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene. | Satokata I | Human genetics | 1992 | PMID: 1339397 |
Text-mined citations for rs1200172747 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.
ClinGen staff contributed the HGVS expression for this variant.