VCV000135282.58 - ClinVar

NM_016169.4(SUFU):c.1018G>T (p.Ala340Ser)

Germline

Classification

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

Benign/Likely benign

12 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_016169.4(SUFU):c.1018G>T (p.Ala340Ser)

Variation ID: 135282 Accession: VCV000135282.58

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q24.32 10: 102599540 (GRCh38) [ NCBI UCSC ] 10: 104359297 (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 9, 2014	Mar 22, 2025	Mar 4, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_016169.4:c.1018G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_057253.2:p.Ala340Ser	missense
NM_001178133.2:c.1018G>T	NP_001171604.1:p.Ala340Ser	missense
NC_000010.11:g.102599540G>T
NC_000010.10:g.104359297G>T
NG_021338.1:g.100579G>T
LRG_521:g.100579G>T
LRG_521t1:c.1018G>T	LRG_521p1:p.Ala340Ser
	Q9UMX1:p.Ala340Ser

... more HGVS ... less HGVS

Protein change

A340S

Other names

Canonical SPDI

NC_000010.11:102599539:G: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.

0.00280 (T)

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

1000 Genomes Project 30x 0.00250

1000 Genomes Project 0.00280

Trans-Omics for Precision Medicine (TOPMed) 0.00553

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00669

The Genome Aggregation Database (gnomAD), exomes 0.00596

Exome Aggregation Consortium (ExAC) 0.00606

The Genome Aggregation Database (gnomAD) 0.00646

Links

ClinGen: CA162213 UniProtKB: Q9UMX1#VAR_021567 dbSNP: rs34135067 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.
SUFU		-	-	GRCh38 GRCh37	1501	1700

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	Likely benign (4)	criteria provided, single submitter	Mar 4, 2025	RCV000122097.18
Medulloblastoma	Likely benign (1)	criteria provided, single submitter	Jan 12, 2018	RCV001103677.12
not provided	Benign/Likely benign (8)	criteria provided, multiple submitters, no conflicts	Feb 1, 2025	RCV000423552.46
Hereditary cancer-predisposing syndrome	Benign (1)	criteria provided, single submitter	Dec 8, 2016	RCV000563391.11
Gorlin syndrome Medulloblastoma	Benign (1)	criteria provided, single submitter	Feb 4, 2025	RCV001082504.17
Familial meningioma Gorlin syndrome Joubert syndrome 32 Medulloblastoma	Benign (1)	criteria provided, single submitter	Jul 26, 2021	RCV002477319.8
Familial meningioma	Benign (1)	criteria provided, single submitter	Feb 1, 2025	RCV005235023.1

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.
Benign (May 25, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000699411.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: Variant summary: The SUFU c.1018G>T (p.Ala340Ser) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a benign outcome. This variant was … (more) Variant summary: The SUFU c.1018G>T (p.Ala340Ser) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a benign outcome. This variant was found in 733/120930 control chromosomes (including 5 homozygotes), predominantly observed in the European (Finnish) subpopulation at a frequency of 0.0105836 (70/6614). This frequency is about 10499 times the estimated maximal expected allele frequency of a pathogenic SUFU variant (0.000001), suggesting this is a benign polymorphism found primarily in the populations of European (Finnish) origin. Taken together, this variant is classified as Benign. (less)
Likely benign (Jan 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Medulloblastoma Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001260469.1 First in ClinVar: May 31, 2020 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Benign (Jan 15, 2020) 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: SCV000522511.6 First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023	Comment: This variant is associated with the following publications: (PMID: 16760173, 28717660, 24728327, 12068298, 21188540, 17102621, 22508808, 28051113)
Benign (Dec 08, 2016) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000675267.5 First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (Feb 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002497078.20 First in ClinVar: Apr 11, 2022 Last updated: Mar 22, 2025	Comment: SUFU: PP2, BP4, BS2 Number of individuals with the variant: 85
Likely Benign (Sep 27, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000511079.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: Converted during submission to Likely benign.
Benign (Jul 26, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Basal cell nevus syndrome 1 Medulloblastoma Familial meningioma Joubert syndrome 32 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002803525.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jun 30, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002046447.3 First in ClinVar: Jan 03, 2022 Last updated: Jan 06, 2024	Publications: PubMed (6) PubMed: 34056767‚ 24728327‚ 12068298‚ 21188540‚ 28717660‚ 17102621
Benign (Aug 25, 2023) 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: SCV001474625.6 First in ClinVar: Jan 26, 2021 Last updated: Feb 20, 2024
Benign (Feb 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Gorlin syndrome Medulloblastoma 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: SCV000290184.11 First in ClinVar: Jul 01, 2016 Last updated: Mar 04, 2025
Likely benign (Mar 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV005872557.1 First in ClinVar: Mar 11, 2025 Last updated: Mar 11, 2025
Benign (Feb 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial meningioma Affected status: no Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV005881347.1 First in ClinVar: Mar 16, 2025 Last updated: Mar 16, 2025
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: SCV001809650.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021
Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not provided 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: SCV001975639.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002037055.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 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: SCV001958758.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
not provided (Sep 19, 2013) N Not contributing to aggregate classification	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000086312.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 Observation 1: Ethnicity/Population group: Whole_cohort Observation 2: Ethnicity/Population group: African Observation 3: Ethnicity/Population group: African_European Observation 4: Ethnicity/Population group: Central_Asian Observation 5: Ethnicity/Population group: East_Asian Observation 6: Ethnicity/Population group: European Observation 7: Ethnicity/Population group: Hispanic
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Comment:

Variant summary: The SUFU c.1018G>T (p.Ala340Ser) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a benign outcome. This variant was found in 733/120930 control chromosomes (including 5 homozygotes), predominantly observed in the European (Finnish) subpopulation at a frequency of 0.0105836 (70/6614). This frequency is about 10499 times the estimated maximal expected allele frequency of a pathogenic SUFU variant (0.000001), suggesting this is a benign polymorphism found primarily in the populations of European (Finnish) origin. Taken together, this variant is classified as Benign.

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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
GAB1 overexpression identifies hedgehog-activated anterior skull base meningiomas.	Boetto J	Neuropathology and applied neurobiology	2021	PMID: 34056767
A novel molecular diagnostics platform for somatic and germline precision oncology.	Cabanillas R	Molecular genetics & genomic medicine	2017	PMID: 28717660
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.	Bodian DL	PloS one	2014	PMID: 24728327
Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma.	Slade I	Familial cancer	2011	PMID: 21188540
Identification and analysis of tumor suppressor loci at chromosome 10q23.3-10q25.3 in medulloblastoma.	Scott DK	Cell cycle (Georgetown, Tex.)	2006	PMID: 17102621
Mutations in SUFU predispose to medulloblastoma.	Taylor MD	Nature genetics	2002	PMID: 12068298

Text-mined citations for rs34135067 ...

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 Mar 22, 2025

ClinVar Genomic variation as it relates to human health

NM_016169.4(SUFU):c.1018G>T (p.Ala340Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs34135067 ...