NM_005236.3(ERCC4):c.145C>T (p.Leu49Phe) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Sep 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001359252.1

Allele description [Variation Report for NM_005236.3(ERCC4):c.145C>T (p.Leu49Phe)]

NM_005236.3(ERCC4):c.145C>T (p.Leu49Phe)

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.145C>T (p.Leu49Phe)
HGVS:
  • NC_000016.10:g.13920310C>T
  • NG_011442.1:g.5154C>T
  • NM_005236.3:c.145C>TMANE SELECT
  • NP_005227.1:p.Leu49Phe
  • LRG_463t1:c.145C>T
  • LRG_463:g.5154C>T
  • NC_000016.9:g.14014167C>T
  • NM_005236.2:c.145C>T
Protein change:
L49F
Links:
Molecular consequence:
  • NM_005236.3:c.145C>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
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 (FANCQ)
Identifiers:
MONDO: MONDO:0014108; MedGen: C3808988; Orphanet: 84; OMIM: 615272

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001555115Invitaecriteria provided, single submitter
Uncertain significance
(Sep 24, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001555115.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces leucine with phenylalanine at codon 49 of the ERCC4 protein (p.Leu49Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs552142099, ExAC 0.005%). This variant has not been reported in the literature in individuals with ERCC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 884829). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.

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

Last Updated: Apr 18, 2021

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