VCV000095660.74 - ClinVar

NM_015046.7(SETX):c.3455T>G (p.Phe1152Cys)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign

11 out of 17 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_015046.7(SETX):c.3455T>G (p.Phe1152Cys)

Variation ID: 95660 Accession: VCV000095660.74

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q34.13 9: 132328143 (GRCh38) [ NCBI UCSC ] 9: 135203530 (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 6, 2014	Apr 13, 2025	Jan 31, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_015046.7:c.3455T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_055861.3:p.Phe1152Cys	missense
NM_001351527.2:c.3455T>G	NP_001338456.1:p.Phe1152Cys	missense
NM_001351528.2:c.3455T>G	NP_001338457.1:p.Phe1152Cys	missense
NC_000009.12:g.132328143A>C
NC_000009.11:g.135203530A>C
NG_007946.1:g.31843T>G
LRG_268:g.31843T>G
LRG_268t1:c.3455T>G	LRG_268p1:p.Phe1152Cys
	Q7Z333:p.Phe1152Cys

... more HGVS ... less HGVS

Protein change

F1152C

Other names

Canonical SPDI

NC_000009.12:132328142:A:C

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.

0.08966 (C)

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

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.03844

The Genome Aggregation Database (gnomAD), exomes 0.04491

The Genome Aggregation Database (gnomAD) 0.04708

The Genome Aggregation Database (gnomAD) 0.05027

Trans-Omics for Precision Medicine (TOPMed) 0.05195

The Genome Aggregation Database (gnomAD), exomes 0.06516

Exome Aggregation Consortium (ExAC) 0.06562

1000 Genomes Project 30x 0.08542

1000 Genomes Project 0.08966

Links

ClinGen: CA148710 UniProtKB: Q7Z333#VAR_018783 dbSNP: rs3739922 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.
SETX		-	-	GRCh38 GRCh37	1950	2034

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 specified	Benign (9)	criteria provided, multiple submitters, no conflicts	Feb 23, 2021	RCV000081693.37
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 8, 2023	RCV000335767.15
Amyotrophic lateral sclerosis type 4	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 8, 2023	RCV000398565.15
Amyotrophic lateral sclerosis type 4 Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Benign (1)	criteria provided, single submitter	Jan 31, 2025	RCV000576443.21
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Nov 26, 2024	RCV001705760.21

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.
Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000312303.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Oct 17, 2018) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001870116.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021	Comment: This variant is associated with the following publications: (PMID: 24694197)
Benign (Feb 08, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Affected status: unknown Allele origin: germline	Genome-Nilou Lab Accession: SCV003931427.1 First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023
Benign (Feb 08, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Amyotrophic lateral sclerosis type 4 Affected status: unknown Allele origin: germline	Genome-Nilou Lab Accession: SCV003931428.1 First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023
benign (Feb 23, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV000677476.2 First in ClinVar: Jan 07, 2018 Last updated: Jan 19, 2025
Benign (Jan 31, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Amyotrophic lateral sclerosis type 4 Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001732203.6 First in ClinVar: Jun 15, 2021 Last updated: Mar 04, 2025
Benign (Nov 26, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000605092.11 First in ClinVar: Oct 02, 2016 Last updated: Mar 11, 2025
Benign (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000477846.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Amyotrophic lateral sclerosis type 4 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000477847.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005319227.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Aug 14, 2012) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000113624.9 First in ClinVar: Jan 23, 2014 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SETX Number of individuals with the variant: 1 Zygosity: Homozygote Sex: mixed
Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	AllHighlyPenetrant Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000152710.2 First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014	Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
Benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001809045.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021
Benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001924725.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001930890.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001963993.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021
Benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001952774.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Comment:

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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SETX	-	-	-	-

Text-mined citations for rs3739922 ...

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 May 17, 2025

ClinVar Genomic variation as it relates to human health

NM_015046.7(SETX):c.3455T>G (p.Phe1152Cys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs3739922 ...