VCV000413910.32 - ClinVar

NM_016169.4(SUFU):c.1245C>T (p.Gly415=)

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.

(6)

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.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(2); Likely benign(2)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_016169.4(SUFU):c.1245C>T (p.Gly415=)

Variation ID: 413910 Accession: VCV000413910.32

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q24.32 10: 102617377 (GRCh38) [ NCBI UCSC ] 10: 104377134 (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	Jan 1, 2018	Oct 20, 2024	Jan 19, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_016169.4:c.1245C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_057253.2:p.Gly415=	synonymous
NM_001178133.2:c.1245C>T	NP_001171604.1:p.Gly415=	synonymous
NC_000010.11:g.102617377C>T
NC_000010.10:g.104377134C>T
NG_021338.1:g.118416C>T
LRG_521:g.118416C>T
LRG_521t1:c.1245C>T	LRG_521p1:p.Gly415=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000010.11:102617376: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.

0.00040 (T)

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

The Genome Aggregation Database (gnomAD), exomes 0.00033

1000 Genomes Project 0.00040

The Genome Aggregation Database (gnomAD) 0.00011

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

Trans-Omics for Precision Medicine (TOPMed) 0.00024

1000 Genomes Project 30x 0.00031

Links

ClinGen: CA5667907 dbSNP: rs144158469 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	1377	1564

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.
Hereditary cancer-predisposing syndrome	Likely benign (1)	criteria provided, single submitter	Apr 13, 2017	RCV000573131.3
not provided	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Oct 1, 2022	RCV000505895.23
Gorlin syndrome Medulloblastoma	Benign (1)	criteria provided, single submitter	Jan 19, 2024	RCV001084319.8
not specified	Benign (1)	criteria provided, single submitter	Aug 26, 2021	RCV002475904.1
SUFU-related disorder	Likely benign (1)	no assertion criteria provided	Apr 27, 2021	RCV004551543.2

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 (Jun 15, 2017)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	Not Provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000605324.2 First in ClinVar: Sep 30, 2017 Last updated: Feb 17, 2019	Comment: The c.1245C>T variant (rs144158469) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. … (more) The c.1245C>T variant (rs144158469) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant does not alter the amino acid sequence of the SUFU protein but computational splice site prediction algorithms predict the creation of a novel splice donor site at this position (Alamut v2.8.1). However, it is uncertain if this new splice site is utilized without functional mRNA studies. This variant is listed in the NHLBI GO Exome Sequencing Project with an overall population frequency of 0.02 percent (identified on 2 out of 13,006 chromosomes) and is listed in the Exome Aggregation Consortium Browser with a Latino population frequency of 0.3 percent (identified on 35 out of 11,578 chromosomes). Altogether, there is not enough evidence to classify the c.1245C>T variant with certainty. (less)
Benign (Aug 26, 2021)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002773992.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jan 19, 2024)	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: SCV000557083.9 First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024
Likely benign (Apr 13, 2017)	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: SCV000675289.5 First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely 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 (Oct 01, 2022)	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: SCV004127287.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: SUFU: BP4, BP7 Number of individuals with the variant: 1
Likely benign (Apr 27, 2021)	no assertion criteria provided Method: clinical testing	SUFU-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004763761.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Comment:

The c.1245C>T variant (rs144158469) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant does not alter the amino acid sequence of the SUFU protein but computational splice site prediction algorithms predict the creation of a novel splice donor site at this position (Alamut v2.8.1). However, it is uncertain if this new splice site is utilized without functional mRNA studies. This variant is listed in the NHLBI GO Exome Sequencing Project with an overall population frequency of 0.02 percent (identified on 2 out of 13,006 chromosomes) and is listed in the Exome Aggregation Consortium Browser with a Latino population frequency of 0.3 percent (identified on 35 out of 11,578 chromosomes). Altogether, there is not enough evidence to classify the c.1245C>T variant with certainty.

Comment:

This alteration is classified as likely 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

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 rs144158469 ...

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 Nov 19, 2024

ClinVar Genomic variation as it relates to human health

NM_016169.4(SUFU):c.1245C>T (p.Gly415=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs144158469 ...