VCV000466241.33 - ClinVar

NM_020964.3(EPG5):c.214G>A (p.Ala72Thr)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(2)

3 out of 6 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_020964.3(EPG5):c.214G>A (p.Ala72Thr)

Variation ID: 466241 Accession: VCV000466241.33

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 18q21.1 18: 45955188 (GRCh38) [ NCBI UCSC ] 18: 43535154 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 26, 2017	Jan 11, 2026	Jan 27, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_020964.3:c.214G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_066015.2:p.Ala72Thr	missense
NC_000018.10:g.45955188C>T
NC_000018.9:g.43535154C>T
NG_042838.1:g.17152G>A
LRG_1234:g.17152G>A
LRG_1234t1:c.214G>A	LRG_1234p1:p.Ala72Thr

... more HGVS ... less HGVS

Protein change

A72T

Other names

Canonical SPDI

NC_000018.10:45955187:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00040 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00031

1000 Genomes Project 0.00040

Trans-Omics for Precision Medicine (TOPMed) 0.00087

The Genome Aggregation Database (gnomAD) 0.00088

The Genome Aggregation Database (gnomAD) 0.00093

The Genome Aggregation Database (gnomAD), exomes 0.00112

Exome Aggregation Consortium (ExAC) 0.00128

The Genome Aggregation Database (gnomAD), exomes 0.00136

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00165

Links

ClinGen: CA8949996 dbSNP: rs201067154 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
EPG5		-	-	GRCh38 GRCh37	2621	2803

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Vici syndrome	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	Jan 27, 2025	RCV000548885.18
not provided	Benign (3)	criteria provided, single submitter	Apr 1, 2024	RCV001706669.19
EPG5-related disorder	Likely benign (1)	no assertion criteria provided	Sep 20, 2022	RCV003935457.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Mar 30, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Vici syndrome	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago Accession: SCV000898670.2 First in ClinVar: Apr 25, 2019 Last updated: May 06, 2023	Comment: show EPG5 NM_020964.2 exon2 p.Ala72Thr (c.214G>A): This variant has not been reported in the literature but is present in 0.3% (86/30602) of South Asian alleles including 2 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/18-43535154-C-T). This variant is present in ClinVar (Variation ID:466241). This variant amino acid threonine (Thr) is present in 4 species (alpaca, platypus, saker falcon, peregrine falcon) and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jan 27, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Vici syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000641813.8 First in ClinVar: Dec 26, 2017 Last updated: Feb 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Apr 01, 2024) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV005041624.16 First in ClinVar: May 12, 2024 Last updated: Jan 11, 2026	Comment: show EPG5: BP4, BS1, BS2 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001931295.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001971524.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Sep 20, 2022) N Not contributing to aggregate classification	no assertion criteria provided	EPG5-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004747585.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

EPG5 NM_020964.2 exon2 p.Ala72Thr (c.214G>A): This variant has not been reported in the literature but is present in 0.3% (86/30602) of South Asian alleles including 2 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/18-43535154-C-T). This variant is present in ClinVar (Variation ID:466241). This variant amino acid threonine (Thr) is present in 4 species (alpaca, platypus, saker falcon, peregrine falcon) and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs201067154 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 11, 2026