VCV000559390.2 - ClinVar

TNRC6A, 5-BP INS, TTTCA(n) REPEAT EXPANSION

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

TNRC6A, 5-BP INS, TTTCA(n) REPEAT EXPANSION

Variation ID: 559390 Accession: VCV000559390.2

Type and length

Microsatellite, -

Location

Cytogenetic: 16p12.1 -

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	Aug 6, 2018	Jun 9, 2024	Mar 21, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000016.10:g.24613440_24613529TTTTA[22]TTTCA[exp]TTTTA[exp]
NC_000016.9:g.24624761_24624850TTTTA[22]TTTCA[exp]TTTTA[exp]

Protein change

Other names

5-BP INS, TTTCA(n)

Canonical SPDI

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

LOVD 3: TNRC6A_000004 OMIM: 610739.0001

Comment on variant

NCBI staff provided an HGVS expression for allelic variant 610739.0001 based on the record in https://www.lovd.nl/TNRC6A.

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.
TNRC6A		-	-	GRCh38 GRCh38 GRCh37	137	170

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.
Epilepsy, familial adult myoclonic, 6	Pathogenic (1)	no assertion criteria provided	Mar 21, 2022	RCV000677095.2

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 (Mar 21, 2022)	no assertion criteria provided Method: literature only	EPILEPSY, FAMILIAL ADULT MYOCLONIC, 6 (1 family) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000802936.2 First in ClinVar: Aug 06, 2018 Last updated: Jun 09, 2024	Publications: PubMed (1) PubMed: 29507423 Comment on evidence: In 5 affected members of a multigenerational Japanese family (F9283) with familial adult myoclonic epilepsy-6 (FAME6; 618074), Ishiura et al. (2018) identified a heterozygous 5-bp … (more) In 5 affected members of a multigenerational Japanese family (F9283) with familial adult myoclonic epilepsy-6 (FAME6; 618074), Ishiura et al. (2018) identified a heterozygous 5-bp TTTCA(n) repeat in the upstream noncoding region of exon 1 of the TNRC6A gene. This expansion was located between two 5-bp TTTTA(n) repeats. TTTCA(n) repeat expansions were not found in the reference sequence or in 1,000 controls individuals. TTTTA(n) expanded repeats were found in 0.9% of controls, suggesting that the TTTCA(n) expansion is responsible for the phenotype. The mutation was found by searching for repeat motifs using data from whole-genome sequence analysis and Southern blot analysis after a similar repeat expansion was identified in the SAMD12 gene (618073) in patients with FAME1. Functional studies of the TNRC6A variant and studies of patient cells were not performed. (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
Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy.	Ishiura H	Nature genetics	2018	PMID: 29507423

Text-mined citations for this variant ...

Record last updated Jun 10, 2024

ClinVar Genomic variation as it relates to human health

TNRC6A, 5-BP INS, TTTCA(n) REPEAT EXPANSION

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...