VCV000517671.22 - ClinVar

NM_002076.4(GNS):c.253-10del

Germline

Classification

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

Benign/Likely benign
Benign (2); Likely benign (1)

3 out of 8 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

Functional data are available for this variant

Variant Details

Identifiers

NM_002076.4(GNS):c.253-10del

Variation ID: 517671 Accession: VCV000517671.22

Type and length

Deletion, 1 bp

Location

Cytogenetic: 12q14.3 12: 64747928 (GRCh38) [ NCBI UCSC ] 12: 65141708 (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	Apr 9, 2018	Feb 23, 2026	Feb 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_002076.4:c.253-10del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_002076.4:c.253-12del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_002076.3:c.253-10del
NC_000012.12:g.64747930del
NC_000012.11:g.65141710del
NG_008955.1:g.16519del

... more HGVS ... less HGVS

Protein change

Other names

NC_000012.11:g.65141710del

Canonical SPDI

NC_000012.12:64747927:AAA:AA

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.

0.00719 (AA)

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

Links

ClinGen: CA6669982 dbSNP: rs201654719 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.
GNS		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	857	873

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 (2)	criteria provided, single submitter	Feb 9, 2017	RCV000614994.3
Mucopolysaccharidosis, MPS-III-D	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 4, 2026	RCV000625327.12
not provided	Likely benign (2)	no assertion criteria provided	Nov 3, 2017	RCV000675670.9
Sanfilippo syndrome	Benign (1)	no assertion criteria provided	Sep 25, 2019	RCV001829732.1

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.	Expand all rows Collapse all rows 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.
Likely benign (Feb 09, 2017) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000732054.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: show This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Sep 21, 2015) C Contributing to aggregate classification	criteria provided, single submitter (ACGS Guidelines, 2013)	Mucopolysaccharidosis, MPS-III-D	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV000744951.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Mucopolysaccharidosis, MPS-III-D	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001095822.8 First in ClinVar: Dec 17, 2019 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Nov 03, 2017) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000801373.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001742900.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Clinical Genetics, Academic Medical Center Study: VKGL Data-share Consensus Accession: SCV001921300.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Sep 25, 2019) N Not contributing to aggregate classification	no assertion criteria provided	Sanfilippo disease	Natera, Inc. Accession: SCV002091726.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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.

Submissions - Functional Data

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0498)

Modifies a natural acceptor site at NC_000012.11:g.65141699 from 11.51 to 10.15 bits. Significant p-values: junction spanning - intron inclusion (2 reads, p=0.0498). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV006567122.1

Submitted: 2025-10-09

Assay description:

In the sample (TCGA-KN-8434), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Nonpapillary renal cell carcinoma
Transcript: NM_002076.4:c.253-12del
Molecular phenotype measured: splicing
Cell line: TCGA-KN-8434
Tissue: Kidney Chromophobe (KICH)
Collection method: in vitro
Species: human
Number of controls: 84

Text-mined citations for rs201654719 ...

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 01, 2026