VCV000430932.2 - ClinVar

NM_004849.4(ATG5):c.366A>T (p.Glu122Asp)

Germline

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.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004849.4(ATG5):c.366A>T (p.Glu122Asp)

Variation ID: 430932 Accession: VCV000430932.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6q21 6: 106279773 (GRCh38) [ NCBI UCSC ] 6: 106727648 (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	Jan 2, 2020	Jan 2, 2020	Feb 1, 2005

HGVS

Nucleotide	Protein	Molecular consequence
NM_004849.4:c.366A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004840.1:p.Glu122Asp	missense
NM_001286106.2:c.366A>T	NP_001273035.1:p.Glu122Asp	missense
NM_001286107.2:c.132A>T	NP_001273036.1:p.Glu44Asp	missense
NM_001286108.2:c.366A>T	NP_001273037.1:p.Glu122Asp	missense
NM_001286111.2:c.109-31529A>T		intron variant
NR_104402.1:n.424A>T		non-coding transcript variant
NR_104403.1:n.296A>T		non-coding transcript variant
NC_000006.12:g.106279773T>A
NC_000006.11:g.106727648T>A

... more HGVS ... less HGVS

Protein change

E122D, E44D

Other names

Canonical SPDI

NC_000006.12:106279772:T:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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.

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

Links

OMIM: 604261.0001 dbSNP: rs1131692265 ClinGen: CA365319959 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.
ATG5		-	-	GRCh38 GRCh37	13	38

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.
Spinocerebellar ataxia, autosomal recessive 25	Pathogenic (1)	no assertion criteria provided	Feb 1, 2005	RCV000496077.2

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.	More information 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.
Pathogenic (Feb 01, 2005)	no assertion criteria provided Method: literature only	SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 25 (1 family) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000584049.2 First in ClinVar: Jul 31, 2017 Last updated: Jan 02, 2020	Publications: PubMed (2) PubMed: 26812546‚ 15981765 Comment on evidence: In 2 brothers, born of remotely consanguineous Turkish parents, with autosomal recessive spinocerebellar ataxia-25 (SCAR25; 617584), Kim et al. (2016) identified a homozygous c.648T-A transversion … (more) In 2 brothers, born of remotely consanguineous Turkish parents, with autosomal recessive spinocerebellar ataxia-25 (SCAR25; 617584), Kim et al. (2016) identified a homozygous c.648T-A transversion (chr6.106,727,648T-A, GRCh37) in the ATG5 gene, resulting in a glu122-to-asp (E122D) substitution at a highly conserved residue in the vicinity of the interaction between ATG5 and ATG12 (609608). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutation was not found in the 1000 Genomes Project, Exome Variant Server, or ExAC databases, or in 500 Turkish control samples. Patient cells showed a reduced interaction between ATG5 and ATG12 and impaired autophagic flux compared to controls. In vitro functional expression studies showed that the E122D mutant protein had normal expression levels, but impaired interaction with ATG12; interaction with ATG16L was not impaired. The findings were consistent with E122D being a hypomorphic allele. The family was originally reported by Yapici and Eraksoy (2005). (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
-	-	-	-	PMID: 15981765
-	-	-	-	PMID: 26812546

Text-mined citations for rs1131692265 ...

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 Apr 25, 2022

ClinVar Genomic variation as it relates to human health

NM_004849.4(ATG5):c.366A>T (p.Glu122Asp)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1131692265 ...