VCV001163312.10 - ClinVar

NM_198252.3(GSN):c.616C>T (p.Arg206Ter)

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.

(4)

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, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_198252.3(GSN):c.616C>T (p.Arg206Ter)

Variation ID: 1163312 Accession: VCV001163312.10

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q33.2 9: 121312441 (GRCh38) [ NCBI UCSC ] 9: 124074719 (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	Jun 15, 2021	Feb 4, 2024	Jul 26, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_198252.3:c.616C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_937895.1:p.Arg206Ter	nonsense
NM_000177.5:c.769C>T	NP_000168.1:p.Arg257Ter	nonsense
NM_001127662.2:c.616C>T	NP_001121134.1:p.Arg206Ter	nonsense
NM_001127663.2:c.724C>T	NP_001121135.2:p.Arg242Ter	nonsense
NM_001127664.2:c.616C>T	NP_001121136.1:p.Arg206Ter	nonsense
NM_001127665.2:c.616C>T	NP_001121137.1:p.Arg206Ter	nonsense
NM_001127666.2:c.649C>T	NP_001121138.1:p.Arg217Ter	nonsense
NM_001127667.2:c.649C>T	NP_001121139.1:p.Arg217Ter	nonsense
NM_001258029.2:c.667C>T	NP_001244958.1:p.Arg223Ter	nonsense
NM_001258030.2:c.640C>T	NP_001244959.1:p.Arg214Ter	nonsense
NM_001353053.1:c.616C>T	NP_001339982.1:p.Arg206Ter	nonsense
NM_001353054.1:c.616C>T	NP_001339983.1:p.Arg206Ter	nonsense
NM_001353055.2:c.616C>T	NP_001339984.1:p.Arg206Ter	nonsense
NM_001353056.2:c.616C>T	NP_001339985.1:p.Arg206Ter	nonsense
NM_001353057.2:c.616C>T	NP_001339986.1:p.Arg206Ter	nonsense
NM_001353058.2:c.616C>T	NP_001339987.1:p.Arg206Ter	nonsense
NM_001353059.2:c.616C>T	NP_001339988.1:p.Arg206Ter	nonsense
NM_001353060.2:c.616C>T	NP_001339989.1:p.Arg206Ter	nonsense
NM_001353061.2:c.616C>T	NP_001339990.1:p.Arg206Ter	nonsense
NM_001353062.1:c.616C>T	NP_001339991.1:p.Arg206Ter	nonsense
NM_001353063.2:c.649C>T	NP_001339992.1:p.Arg217Ter	nonsense
NM_001353064.2:c.649C>T	NP_001339993.1:p.Arg217Ter	nonsense
NM_001353065.2:c.649C>T	NP_001339994.1:p.Arg217Ter	nonsense
NM_001353066.2:c.649C>T	NP_001339995.1:p.Arg217Ter	nonsense
NM_001353067.2:c.649C>T	NP_001339996.1:p.Arg217Ter	nonsense
NM_001353068.2:c.649C>T	NP_001339997.1:p.Arg217Ter	nonsense
NM_001353069.2:c.649C>T	NP_001339998.1:p.Arg217Ter	nonsense
NM_001353070.2:c.649C>T	NP_001339999.1:p.Arg217Ter	nonsense
NM_001353071.2:c.649C>T	NP_001340000.1:p.Arg217Ter	nonsense
NM_001353072.2:c.649C>T	NP_001340001.1:p.Arg217Ter	nonsense
NM_001353073.2:c.649C>T	NP_001340002.1:p.Arg217Ter	nonsense
NM_001353074.2:c.649C>T	NP_001340003.1:p.Arg217Ter	nonsense
NM_001353075.1:c.649C>T	NP_001340004.1:p.Arg217Ter	nonsense
NM_001353076.2:c.688C>T	NP_001340005.1:p.Arg230Ter	nonsense
NM_001353077.1:c.649C>T	NP_001340006.1:p.Arg217Ter	nonsense
NM_001353078.2:c.-39C>T		5 prime UTR
NC_000009.12:g.121312441C>T
NC_000009.11:g.124074719C>T
NG_012872.2:g.116360C>T

... more HGVS ... less HGVS

Protein change

R206*, R214*, R217*, R223*, R230*, R242*, R257*

Other names

Canonical SPDI

NC_000009.12:121312440: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.

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00006

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Exome Aggregation Consortium (ExAC) 0.00009

Links

dbSNP: rs376060588 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.
GSN		-	-	GRCh38 GRCh37	723	759

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.
not provided	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Mar 2, 2022	RCV001508266.8
Finnish type amyloidosis	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jul 26, 2023	RCV002488308.3

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 (Dec 24, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV001714313.1 First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021	Number of individuals with the variant: 1
Uncertain significance (May 12, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Finnish type amyloidosis Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002781260.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Mar 02, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002288042.2 First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023	Comment: This sequence change creates a premature translational stop signal (p.Arg257) in the GSN gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Arg257) in the GSN gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in GSN cause disease. This variant is present in population databases (rs376060588, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GSN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1163312). 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. (less)
Uncertain significance (Jul 26, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Finnish type amyloidosis Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV004235215.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024

Comment:

This sequence change creates a premature translational stop signal (p.Arg257*) in the GSN gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in GSN cause disease. This variant is present in population databases (rs376060588, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GSN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1163312). 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.

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 rs376060588 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_198252.3(GSN):c.616C>T (p.Arg206Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs376060588 ...