VCV001033174.6 - ClinVar

NM_153816.6(SNX14):c.2395C>T (p.Arg799Trp)

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_153816.6(SNX14):c.2395C>T (p.Arg799Trp)

Variation ID: 1033174 Accession: VCV001033174.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6q14.3 6: 85514232 (GRCh38) [ NCBI UCSC ] 6: 86223950 (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	Mar 22, 2021	Feb 20, 2024	Aug 11, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_153816.6:c.2395C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_722523.1:p.Arg799Trp	missense
NM_001297614.3:c.2368C>T	NP_001284543.1:p.Arg790Trp	missense
NM_001304479.2:c.2239C>T	NP_001291408.1:p.Arg747Trp	missense
NM_001350532.2:c.2458C>T	NP_001337461.1:p.Arg820Trp	missense
NM_001350533.2:c.2392C>T	NP_001337462.1:p.Arg798Trp	missense
NM_001350534.2:c.2365C>T	NP_001337463.1:p.Arg789Trp	missense
NM_001350535.2:c.2392C>T	NP_001337464.1:p.Arg798Trp	missense
NM_001350536.2:c.2263C>T	NP_001337465.1:p.Arg755Trp	missense
NM_001350537.2:c.2260C>T	NP_001337466.1:p.Arg754Trp	missense
NM_001350538.2:c.2251C>T	NP_001337467.1:p.Arg751Trp	missense
NM_001350539.2:c.2236C>T	NP_001337468.1:p.Arg746Trp	missense
NM_001350540.2:c.2392+274C>T		intron variant
NM_001350541.2:c.2365+274C>T		intron variant
NM_001350542.2:c.2107C>T	NP_001337471.1:p.Arg703Trp	missense
NM_001350543.2:c.2104C>T	NP_001337472.1:p.Arg702Trp	missense
NM_001350544.2:c.2095C>T	NP_001337473.1:p.Arg699Trp	missense
NM_001350545.2:c.1951C>T	NP_001337474.1:p.Arg651Trp	missense
NM_001350546.2:c.1951C>T	NP_001337475.1:p.Arg651Trp	missense
NM_001350547.2:c.1345C>T	NP_001337476.1:p.Arg449Trp	missense
NM_001350548.2:c.1240C>T	NP_001337477.1:p.Arg414Trp	missense
NM_001350549.2:c.1240C>T	NP_001337478.1:p.Arg414Trp	missense
NM_001350550.2:c.1240C>T	NP_001337479.1:p.Arg414Trp	missense
NM_001350551.2:c.1240C>T	NP_001337480.1:p.Arg414Trp	missense
NM_001350552.2:c.1240C>T	NP_001337481.1:p.Arg414Trp	missense
NM_001350553.2:c.1213C>T	NP_001337482.1:p.Arg405Trp	missense
NM_020468.6:c.2236C>T	NP_065201.1:p.Arg746Trp	missense
NR_146774.2:n.2277C>T		non-coding transcript variant
NR_146775.2:n.2280C>T		non-coding transcript variant
NR_146776.2:n.2403C>T		non-coding transcript variant
NR_146777.2:n.2531C>T		non-coding transcript variant
NR_146778.2:n.2535C>T		non-coding transcript variant
NR_146779.2:n.2532C>T		non-coding transcript variant
NC_000006.12:g.85514232G>A
NC_000006.11:g.86223950G>A
NG_047171.1:g.84925C>T

... more HGVS ... less HGVS

Protein change

R651W, R699W, R703W, R746W, R754W, R449W, R747W, R755W, R790W, R405W, R414W, R751W, R820W, R702W, R789W, R798W, R799W

Other names

Canonical SPDI

NC_000006.12:85514231:G: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.

0.00060 (A)

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

The Genome Aggregation Database (gnomAD) 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00023

Exome Aggregation Consortium (ExAC) 0.00029

1000 Genomes Project 0.00060

1000 Genomes Project 30x 0.00062

Links

dbSNP: rs556044910 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.
SNX14		-	-	GRCh38 GRCh37	289	311

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 recessive spinocerebellar ataxia 20	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jul 28, 2021	RCV001335507.2
not provided	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Aug 11, 2022	RCV001751655.5

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 (Feb 16, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive spinocerebellar ataxia 20 Affected status: yes Allele origin: maternal	Baylor Genetics Accession: SCV001528671.1 First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021	Comment: This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Uncertain significance (Oct 04, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001996187.2 First in ClinVar: Nov 06, 2021 Last updated: Mar 04, 2023	Comment: In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our … (more) In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge (less)
Uncertain significance (Jul 28, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive spinocerebellar ataxia 20 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002777160.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Aug 11, 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: SCV003477227.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024	Comment: This variant is present in population databases (rs556044910, gnomAD 0.2%). In summary, the available evidence is currently insufficient to determine the role of this variant … (more) This variant is present in population databases (rs556044910, gnomAD 0.2%). 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1033174). This variant has not been reported in the literature in individuals affected with SNX14-related conditions. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 799 of the SNX14 protein (p.Arg799Trp). (less)

Comment:

This variant is present in population databases (rs556044910, gnomAD 0.2%). 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1033174). This variant has not been reported in the literature in individuals affected with SNX14-related conditions. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 799 of the SNX14 protein (p.Arg799Trp).

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 rs556044910 ...

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_153816.6(SNX14):c.2395C>T (p.Arg799Trp)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs556044910 ...