NM_020964.3(EPG5):c.3014C>T (p.Thr1005Met) AND Vici syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 22, 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:: RCV000805037.10

Allele description [Variation Report for NM_020964.3(EPG5):c.3014C>T (p.Thr1005Met)]

NM_020964.3(EPG5):c.3014C>T (p.Thr1005Met)

Gene:

EPG5:ectopic P-granules 5 autophagy tethering factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.1

Genomic location:

Preferred name:

NM_020964.3(EPG5):c.3014C>T (p.Thr1005Met)

HGVS:

NC_000018.10:g.45922425G>A
NG_042838.1:g.49915C>T
NM_020964.3:c.3014C>TMANE SELECT
NP_066015.2:p.Thr1005Met
LRG_1234t1:c.3014C>T
LRG_1234:g.49915C>T
LRG_1234p1:p.Thr1005Met
NC_000018.9:g.43502391G>A
NM_020964.2:c.3014C>T

Protein change:

T1005M

Links:

dbSNP: rs890699630

NCBI 1000 Genomes Browser:

rs890699630

Molecular consequence:

NM_020964.3:c.3014C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Vici syndrome (VICIS)
Identifiers:: MONDO: MONDO:0009452; MedGen: C1855772; Orphanet: 1493; OMIM: 242840

Recent activity

Clear Turn Off Turn On

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
SCV000944979	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001480413	New York Genome Center - CSER-NYCKidSeq	criteria provided, single submitter (NYGC Assertion Criteria 2020)	Uncertain significance (May 12, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000944979

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 2022)

germline

clinical testing

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

SCV001480413

New York Genome Center - CSER-NYCKidSeq

criteria provided, single submitter

(NYGC Assertion Criteria 2020)

Uncertain significance
(May 12, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	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, SCV000944979.5

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

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1005 of the EPG5 protein (p.Thr1005Met). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 649976). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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 New York Genome Center - CSER-NYCKidSeq, SCV001480413.1

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

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

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine