NM_000082.4(ERCC8):c.479C>T (p.Ala160Val) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Dec 2, 2023
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:: RCV000059647.12

Allele description [Variation Report for NM_000082.4(ERCC8):c.479C>T (p.Ala160Val)]

NM_000082.4(ERCC8):c.479C>T (p.Ala160Val)

Gene:

ERCC8:ERCC excision repair 8, CSA ubiquitin ligase complex subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q12.1

Genomic location:

Preferred name:

NM_000082.4(ERCC8):c.479C>T (p.Ala160Val)

HGVS:

NC_000005.10:g.60904794G>A
NG_009289.1:g.45285C>T
NM_000082.4:c.479C>TMANE SELECT
NM_001007233.3:c.305C>T
NM_001007234.3:c.479C>T
NM_001290285.2:c.23-1078C>T
NP_000073.1:p.Ala160Val
NP_000073.1:p.Ala160Val
NP_001007234.1:p.Ala102Val
NP_001007235.1:p.Ala160Val
LRG_466t1:c.479C>T
LRG_466:g.45285C>T
LRG_466p1:p.Ala160Val
NC_000005.9:g.60200621G>A
NM_000082.3:c.479C>T
Q13216:p.Ala160Val

Protein change:

A102V; ALA160VAL

Links:

UniProtKB: Q13216#VAR_025380; UniProtKB/Swiss-Prot: VAR_025380; OMIM: 609412.0004; dbSNP: rs121434325

NCBI 1000 Genomes Browser:

rs121434325

Molecular consequence:

NM_001290285.2:c.23-1078C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000082.4:c.479C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001007233.3:c.305C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001007234.3:c.479C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

mitochondrial carnitine/acylcarnitine carrier protein-like isoform X1 [Oreochrom...
mitochondrial carnitine/acylcarnitine carrier protein-like isoform X1 [Oreochromis aureus]
gi|1779292962|ref|XP_031612982.1|

Protein
carboxy terminal-processing peptidase [Planctellipticum variicoloris]
carboxy terminal-processing peptidase [Planctellipticum variicoloris]
gi|2557462154|gnl|extdb|SH412_00333 WLD13176.1|

Protein

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
SCV000091217	UniProtKB/Swiss-Prot	no classification provided	not provided	not provided	not provided	PubMed (1) [See all records that cite this PMID]
SCV000521089	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Mar 26, 2021)	germline	clinical testing	Citation Link,
SCV001575796	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 2, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29572252, 15744458, 28492532
SCV002520026	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 12, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 15744458, 18695064, 29572252, 29742419, 32048102, 33199595, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

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

Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects.

Ridley AJ, Colley J, Wynford-Thomas D, Jones CJ.

J Hum Genet. 2005;50(3):151-154. doi: 10.1007/s10038-004-0228-2. Epub 2005 Mar 3.

PubMed [citation]

PMID:: 15744458

See all PubMed Citations (8)

Details of each submission

From UniProtKB/Swiss-Prot, SCV000091217.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV000521089.4

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

Description

Identified in the presence of a second ERCC8 variant, phase unknown, in a patient with Cockayne syndrome (Ridley et al., 2005).; Published studies demonstrate a damaging effect; specifically, this variant causes the deletion of exon 5 in the transcipt (Nardo et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29742419, 19329487, 15744458, 29572252, 33199595)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001575796.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 160 of the ERCC8 protein (p.Ala160Val). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs121434325, gnomAD 0.002%). This missense change has been observed in individual(s) with Cockayne syndrome type A (PMID: 15744458, 29572252). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1717). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change results in deletion of exon 5 and introduces a premature termination codon (PMID: 15744458). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV002520026.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

PP3, PP4, PM2, PM3, PM5, PS4_moderate

#	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