VCV000135472.17 - ClinVar

NM_004628.5(XPC):c.2782A>C (p.Lys928Gln)

Germline

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.

(6)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004628.5(XPC):c.2782A>C (p.Lys928Gln)

Variation ID: 135472 Accession: VCV000135472.17

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p25.1 3: 14145982 (GRCh38) [ NCBI UCSC ] 3: 14187482 (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	Jun 9, 2014	Oct 8, 2024	Jan 25, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_004628.5:c.2782A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004619.3:p.Lys928Gln	missense
NM_001354726.2:c.2203A>C	NP_001341655.1:p.Lys735Gln	missense
NM_001354727.2:c.2776A>C	NP_001341656.1:p.Lys926Gln	missense
NM_001354729.2:c.2764A>C	NP_001341658.1:p.Lys922Gln	missense
NM_001354730.2:c.2536A>C	NP_001341659.1:p.Lys846Gln	missense
NR_148950.2:n.2654A>C		non-coding transcript variant
NR_148951.2:n.2530A>C		non-coding transcript variant
NC_000003.12:g.14145982T>G
NC_000003.11:g.14187482T>G
NG_011763.1:g.37691A>C
LRG_472:g.37691A>C
LRG_472t1:c.2782A>C	LRG_472p1:p.Lys928Gln
	Q01831:p.Lys928Gln

... more HGVS ... less HGVS

Protein change

K928Q, K735Q, K846Q, K922Q, K926Q

Other names

Canonical SPDI

NC_000003.12:14145981:T:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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.

0.00280 (G)

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

The Genome Aggregation Database (gnomAD), exomes 0.00056

Exome Aggregation Consortium (ExAC) 0.00063

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00190

1000 Genomes Project 0.00280

The Genome Aggregation Database (gnomAD) 0.00285

Trans-Omics for Precision Medicine (TOPMed) 0.00294

1000 Genomes Project 30x 0.00390

Links

ClinGen: CA162874 UniProtKB: Q01831#VAR_018904 dbSNP: rs3731177 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		-	-	GRCh38 GRCh37	989	1098

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 specified	not provided (1)	no classification provided	Sep 19, 2013	RCV000122330.1
not provided	Likely benign (1)	criteria provided, single submitter	Jan 25, 2024	RCV000861084.9
Xeroderma pigmentosum, group C	Benign (2)	criteria provided, multiple submitters, no conflicts	Dec 5, 2021	RCV001150525.5
Xeroderma pigmentosum	Likely benign (1)	criteria provided, single submitter	Nov 17, 2020	RCV002257446.1
XPC-related disorder	Benign (1)	no assertion criteria provided	Aug 14, 2024	RCV003905170.2

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.
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Xeroderma pigmentosum, group C Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001311598.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Publications: PubMed (1) PubMed: 24728327 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
Likely benign (Nov 17, 2020)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Xeroderma pigmentosum Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002537512.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Likely benign (Jan 25, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001001303.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Benign (Dec 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Xeroderma pigmentosum, group C Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002513993.1 First in ClinVar: May 21, 2022 Last updated: May 21, 2022
Benign (Aug 14, 2024)	no assertion criteria provided Method: clinical testing	XPC-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004731072.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
not provided (Sep 19, 2013)	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000086560.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 Observation 1: Ethnicity/Population group: Whole_cohort Observation 2: Ethnicity/Population group: African Observation 3: Ethnicity/Population group: African_European Observation 4: Ethnicity/Population group: Central_Asian Observation 5: Ethnicity/Population group: East_Asian Observation 6: Ethnicity/Population group: European Observation 7: Ethnicity/Population group: Hispanic

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.	Bodian DL	PloS one	2014	PMID: 24728327

Text-mined citations for rs3731177 ...

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 Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_004628.5(XPC):c.2782A>C (p.Lys928Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs3731177 ...