NM_005236.3(ERCC4):c.1787C>A (p.Ala596Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 2022
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:: RCV000820566.7

Allele description [Variation Report for NM_005236.3(ERCC4):c.1787C>A (p.Ala596Glu)]

NM_005236.3(ERCC4):c.1787C>A (p.Ala596Glu)

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.1787C>A (p.Ala596Glu)

HGVS:

NC_000016.10:g.13935719C>A
NG_011442.1:g.20563C>A
NM_005236.3:c.1787C>AMANE SELECT
NP_005227.1:p.Ala596Glu
NP_005227.1:p.Ala596Glu
LRG_463t1:c.1787C>A
LRG_463:g.20563C>A
LRG_463p1:p.Ala596Glu
NC_000016.9:g.14029576C>A
NM_005236.2:c.1787C>A

Protein change:

A596E

Links:

dbSNP: rs751782722

NCBI 1000 Genomes Browser:

rs751782722

Molecular consequence:

NM_005236.3:c.1787C>A - 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

Name:: Cockayne syndrome
Synonyms:: Cockayne's syndrome; Dwarfism-retinal atrophy-deafness syndrome; Progeria-like syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0016006; MedGen: C0009207

Name:: Fanconi anemia complementation group Q
Identifiers:: MONDO: MONDO:0014108; MedGen: C3808988; Orphanet: 84; OMIM: 615272

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000961283	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000961283

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 13, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000961283.4

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ERCC4 protein function. ClinVar contains an entry for this variant (Variation ID: 662825). This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. This variant is present in population databases (rs751782722, gnomAD 0.04%). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 596 of the ERCC4 protein (p.Ala596Glu).

#	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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