NM_000122.2(ERCC3):c.1451T>C (p.Ile484Thr) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 19, 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:: RCV002050187.6

Allele description [Variation Report for NM_000122.2(ERCC3):c.1451T>C (p.Ile484Thr)]

NM_000122.2(ERCC3):c.1451T>C (p.Ile484Thr)

Gene:

ERCC3:ERCC excision repair 3, TFIIH core complex helicase subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q14.3

Genomic location:

Preferred name:

NM_000122.2(ERCC3):c.1451T>C (p.Ile484Thr)

HGVS:

NC_000002.12:g.127280523A>G
NG_007454.1:g.18654T>C
NM_000122.2:c.1451T>CMANE SELECT
NM_001303416.2:c.1259T>C
NM_001303418.2:c.1259T>C
NP_000113.1:p.Ile484Thr
NP_001290345.1:p.Ile420Thr
NP_001290347.1:p.Ile420Thr
LRG_462:g.18654T>C
NC_000002.11:g.128038099A>G

Protein change:

I420T

Links:

dbSNP: rs371767613

NCBI 1000 Genomes Browser:

rs371767613

Molecular consequence:

NM_000122.2:c.1451T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001303416.2:c.1259T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001303418.2:c.1259T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

PREDICTED: Homo sapiens G-patch domain containing 2 (GPATCH2), transcript varian...
PREDICTED: Homo sapiens G-patch domain containing 2 (GPATCH2), transcript variant X3, mRNA
gi|2462510669|ref|XM_054337319.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002109169	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 19, 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

SCV002109169

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 19, 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, SCV002109169.3

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1346717). This missense change has been observed in individual(s) with clinical features of xeroderma pigmentosum/Cockayne syndrome (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs371767613, gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 484 of the ERCC3 protein (p.Ile484Thr).

#	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

ClinVar

Relating variation to medicine