VCV002136613.2 - ClinVar

NM_012470.4(TNPO3):c.2453G>A (p.Arg818Gln)

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_012470.4(TNPO3):c.2453G>A (p.Arg818Gln)

Variation ID: 2136613 Accession: VCV002136613.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q32.1 7: 128970293 (GRCh38) [ NCBI UCSC ] 7: 128610347 (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	Feb 8, 2023	Feb 14, 2024	Mar 1, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_012470.4:c.2453G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_036602.1:p.Arg818Gln	missense
NM_001191028.3:c.2261G>A	NP_001177957.2:p.Arg754Gln	missense
NM_001382216.1:c.2555G>A	NP_001369145.1:p.Arg852Gln	missense
NM_001382217.1:c.2534G>A	NP_001369146.1:p.Arg845Gln	missense
NM_001382218.1:c.2453G>A	NP_001369147.1:p.Arg818Gln	missense
NM_001382219.1:c.2345G>A	NP_001369148.1:p.Arg782Gln	missense
NM_001382220.1:c.2312G>A	NP_001369149.1:p.Arg771Gln	missense
NM_001382221.1:c.2309G>A	NP_001369150.1:p.Arg770Gln	missense
NM_001382222.1:c.2306G>A	NP_001369151.1:p.Arg769Gln	missense
NM_001382223.1:c.2261G>A	NP_001369152.1:p.Arg754Gln	missense
NR_034053.3:n.2955G>A		non-coding transcript variant
NR_167911.1:n.3042G>A		non-coding transcript variant
NR_167912.1:n.2900G>A		non-coding transcript variant
NR_167913.1:n.2702G>A		non-coding transcript variant
NR_167914.1:n.2862G>A		non-coding transcript variant
NR_167915.1:n.3118G>A		non-coding transcript variant
NR_167916.1:n.2592G>A		non-coding transcript variant
NR_167917.1:n.2625G>A		non-coding transcript variant
NR_167918.1:n.3080G>A		non-coding transcript variant
NR_167919.1:n.2919G>A		non-coding transcript variant
NR_167920.1:n.2878G>A		non-coding transcript variant
NR_167921.1:n.3080G>A		non-coding transcript variant
NR_167922.1:n.2916G>A		non-coding transcript variant
NR_167923.1:n.2717G>A		non-coding transcript variant
NR_167924.1:n.2794G>A		non-coding transcript variant
NR_167925.1:n.2717G>A		non-coding transcript variant
NR_167926.1:n.2728G>A		non-coding transcript variant
NR_167927.1:n.3021G>A		non-coding transcript variant
NC_000007.14:g.128970293C>T
NC_000007.13:g.128610347C>T
NG_023428.1:g.89881G>A

... more HGVS ... less HGVS

Protein change

R771Q, R852Q, R754Q, R782Q, R770Q, R845Q, R769Q, R818Q

Other names

Canonical SPDI

NC_000007.14:128970292:C:T

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.
TNPO3		-	-	GRCh38 GRCh37	615	674

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.
Autosomal dominant limb-girdle muscular dystrophy type 1F	Uncertain significance (1)	criteria provided, single submitter	Mar 1, 2022	RCV003062142.3

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 (Mar 01, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Autosomal dominant limb-girdle muscular dystrophy type 1F Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003440172.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024	Publications: PubMed (2) PubMed: 30567601‚ 23667635 Comment: 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 … (more) 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. Experimental studies have shown that this missense change does not substantially affect TNPO3 function (PMID: 30567601). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 23667635). This variant is present in population databases (rs587777431, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 818 of the TNPO3 protein (p.Arg818Gln). (less)

Comment:

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. Experimental studies have shown that this missense change does not substantially affect TNPO3 function (PMID: 30567601). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 23667635). This variant is present in population databases (rs587777431, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 818 of the TNPO3 protein (p.Arg818Gln).

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

Title	Author	Journal	Year	Link
Long term follow-up and further molecular and histopathological studies in the LGMD1F sporadic TNPO3-mutated patient.	Gibertini S	Acta neuropathologica communications	2018	PMID: 30567601
Next-generation sequencing identifies transportin 3 as the causative gene for LGMD1F.	Torella A	PloS one	2013	PMID: 23667635

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_012470.4(TNPO3):c.2453G>A (p.Arg818Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...