VCV003251966.1 - ClinVar

NM_152263.4(TPM3):c.458_459insTAG (p.Lys153delinsAsnArg)

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_152263.4(TPM3):c.458_459insTAG (p.Lys153delinsAsnArg)

Variation ID: 3251966 Accession: VCV003251966.1

Type and length

Insertion, 3 bp

Location

Cytogenetic: 1q21.3 1: 154173120-154173121 (GRCh38) [ NCBI UCSC ] 1: 154145596-154145597 (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	Jul 15, 2024	Jul 15, 2024	Apr 5, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_152263.4:c.458_459insTAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_689476.2:p.Lys153delinsAsnArg	inframe indel
NM_001043351.2:c.347_348insTAG	NP_001036816.1:p.Lys116delinsAsnArg	inframe indel
NM_001043352.2:c.347_348insTAG	NP_001036817.1:p.Lys116delinsAsnArg	inframe indel
NM_001043353.2:c.347_348insTAG	NP_001036818.1:p.Lys116delinsAsnArg	inframe indel
NM_001278188.2:c.149_150insTAG	NP_001265117.1:p.Lys50delinsAsnArg	inframe indel
NM_001278189.2:c.347_348insTAG	NP_001265118.1:p.Lys116delinsAsnArg	inframe indel
NM_001278190.2:c.347_348insTAG	NP_001265119.1:p.Lys116delinsAsnArg	inframe indel
NM_001278191.2:c.77_78insTAG	NP_001265120.1:p.Lys26delinsAsnArg	inframe indel
NM_001349679.2:c.347_348insTAG	NP_001336608.1:p.Lys116delinsAsnArg	inframe indel
NM_001364679.2:c.458_459insTAG	NP_001351608.1:p.Lys153delinsAsnArg	inframe indel
NM_001364680.2:c.458_459insTAG	NP_001351609.1:p.Lys153delinsAsnArg	inframe indel
NM_001364681.2:c.458_459insTAG	NP_001351610.1:p.Lys153delinsAsnArg	inframe indel
NM_001364682.1:c.458_459insTAG	NP_001351611.1:p.Lys153delinsAsnArg	inframe indel
NM_001364683.1:c.347_348insTAG	NP_001351612.1:p.Lys116delinsAsnArg	inframe indel
NM_153649.4:c.347_348insTAG	NP_705935.1:p.Lys116delinsAsnArg	inframe indel
NR_103461.2:n.446_447insTAG		non-coding transcript variant
NC_000001.11:g.154173120_154173121insCTA
NC_000001.10:g.154145596_154145597insCTA
NG_008621.1:g.24013_24014insTAG
LRG_681:g.24013_24014insTAG
LRG_681t1:c.347_348insTAG	LRG_681p1:p.Lys116delinsAsnArg
LRG_681t2:c.458_459insTAG	LRG_681p2:p.Lys153delinsAsnArg
LRG_681t3:c.347_348insTAG	LRG_681p3:p.Lys116delinsAsnArg

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000001.11:154173120::CTA

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

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.
TPM3		-	-	GRCh38 GRCh37	368	387

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.
Congenital myopathy 4A, autosomal dominant	Uncertain significance (1)	criteria provided, single submitter	Apr 5, 2024	RCV004586410.1

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.
Uncertain significance (Apr 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Congenital myopathy 4A, autosomal dominant Affected status: yes Allele origin: unknown	Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology Accession: SCV005077767.1 First in ClinVar: Jul 15, 2024 Last updated: Jul 15, 2024	Comment: The c.458_459insTAG variant is not present in publicly available population databases like 1000 Genomes, EVS, ExAC, gnomAD, Indian Exome Database or our in-house exome database. … (more) The c.458_459insTAG variant is not present in publicly available population databases like 1000 Genomes, EVS, ExAC, gnomAD, Indian Exome Database or our in-house exome database. This variant has neither been published in the literature in individuals with TPM3-related conditions nor reported to the clinical databases like Human Genome Mutation Database (HGMD), ClinVar or OMIM, in any affected individuals. In-silico pathogenicity prediction programs like MutationTaster2, CADD, Varsome etc predicted this variant to be likely deleterious, however these predictions were not confirmed by published functional studies. This variant is located in a mutational hotspot, non-repeat region of the gene that causes in-frame insertion of two new amino acids (asparagine & arginine), in-place of a single amino acid (lysine). (less) Number of individuals with the variant: 1 Zygosity: Single Heterozygote Secondary finding: no Method: exome sequencing

Comment:

The c.458_459insTAG variant is not present in publicly available population databases like 1000 Genomes, EVS, ExAC, gnomAD, Indian Exome Database or our in-house exome database. This variant has neither been published in the literature in individuals with TPM3-related conditions nor reported to the clinical databases like Human Genome Mutation Database (HGMD), ClinVar or OMIM, in any affected individuals. In-silico pathogenicity prediction programs like MutationTaster2, CADD, Varsome etc predicted this variant to be likely deleterious, however these predictions were not confirmed by published functional studies. This variant is located in a mutational hotspot, non-repeat region of the gene that causes in-frame insertion of two new amino acids (asparagine & arginine), in-place of a single amino acid (lysine).

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.

Comment:

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 this variant ...

Record last updated Jul 29, 2024

ClinVar Genomic variation as it relates to human health

NM_152263.4(TPM3):c.458_459insTAG (p.Lys153delinsAsnArg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...