U.S. flag

An official website of the United States government

NM_005236.3(ERCC4):c.1728A>T (p.Arg576Ser) AND Xeroderma pigmentosum, group F

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Mar 10, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000351813.9

Allele description [Variation Report for NM_005236.3(ERCC4):c.1728A>T (p.Arg576Ser)]

NM_005236.3(ERCC4):c.1728A>T (p.Arg576Ser)

Gene:
ERCC4:ERCC excision repair 4, endonuclease catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.12
Genomic location:
Preferred name:
NM_005236.3(ERCC4):c.1728A>T (p.Arg576Ser)
HGVS:
  • NC_000016.10:g.13935660A>T
  • NG_011442.1:g.20504A>T
  • NM_005236.3:c.1728A>TMANE SELECT
  • NP_005227.1:p.Arg576Ser
  • NP_005227.1:p.Arg576Ser
  • LRG_463t1:c.1728A>T
  • LRG_463:g.20504A>T
  • LRG_463p1:p.Arg576Ser
  • NC_000016.9:g.14029517A>T
  • NM_005236.2:c.1728A>T
Protein change:
R576S
Links:
dbSNP: rs765454246
NCBI 1000 Genomes Browser:
rs765454246
Molecular consequence:
  • NM_005236.3:c.1728A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Xeroderma pigmentosum, group F (XPF)
Synonyms:
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F; XERODERMA PIGMENTOSUM VI; XP, GROUP F; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010215; MedGen: C0268140; OMIM: 278760

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000394875Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)
Uncertain significance
(Jan 13, 2018)
germlineclinical testing

Citation Link,

SCV002526100St. Jude Molecular Pathology, St. Jude Children's Research Hospital
criteria provided, single submitter

(St. Jude Assertion Criteria 2020)
Uncertain significance
(Mar 10, 2022)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000394875.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV002526100.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ERCC4 c.1728A>T (p.Arg576Ser) missense change has a maximum subpopulation frequency of 0.014% in gnomAD v2.1.1 ( https://gnomad.broadinstitute.org/variant/16-14029517-A-T ). Six of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. This variant has been reported in an individual with serous cystadenoma (PMID: 28767289). The variant has been identified in 1 of 1358 control individuals collected as part of non-cancer studies (PMID: 29641532). To our knowledge, this variant has not been reported in individuals with Fanconi anemia or Xeroderma pigmentosum. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024