ClinVar Genomic variation as it relates to human health
NM_004646.4(NPHS1):c.802C>T (p.Arg268Ter)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004646.4(NPHS1):c.802C>T (p.Arg268Ter)
Variation ID: 496273 Accession: VCV000496273.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19q13.12 19: 35849274 (GRCh38) [ NCBI UCSC ] 19: 36340176 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 17, 2018 Sep 29, 2024 Mar 18, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004646.4:c.802C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004637.1:p.Arg268Ter nonsense NC_000019.10:g.35849274G>A NC_000019.9:g.36340176G>A NG_013356.2:g.25014C>T NG_051206.1:g.2640G>A LRG_693:g.25014C>T LRG_693t1:c.802C>T LRG_693p1:p.Arg268Ter - Protein change
- R268*
- Other names
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- Canonical SPDI
- NC_000019.10:35849273:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD) 0.00006
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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NPHS1 | - | - |
GRCh38 GRCh37 |
1670 | 1853 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 18, 2024 | RCV000587459.5 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 6, 2024 | RCV003558448.3 |
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
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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
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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. |
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Pathogenic
(Jul 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Finnish congenital nephrotic syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698509.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The NPHS1 c.802C>T (p.Arg268X) variant results in a premature termination codon, predicted to cause a truncated or absent NPHS1 protein due to nonsense … (more)
Variant summary: The NPHS1 c.802C>T (p.Arg268X) variant results in a premature termination codon, predicted to cause a truncated or absent NPHS1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 4/118618 control chromosomes at a frequency of 0.0000337, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPHS1 variant (0.0033541). This variant has been reported in at least 3 NS patients both in compound heterozygosity and homozygously. Taken together, the variant was classified as Pathogenic. (less)
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Pathogenic
(Dec 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004297312.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg268*) in the NPHS1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg268*) in the NPHS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHS1 are known to be pathogenic (PMID: 11317351, 11854170, 12039988). This variant is present in population databases (rs749341977, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with nephrotic syndrome (PMID: 19423745, 28204945). ClinVar contains an entry for this variant (Variation ID: 496273). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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Finnish congenital nephrotic syndrome
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004191402.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Jul 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005197013.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Likely pathogenic
(Feb 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV005324890.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene … (more)
Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 31589614, 19423745, 20507940, 28204945, 30594156, 33980730, 34859019) (less)
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Pathogenic
(Oct 08, 2021)
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no assertion criteria provided
Method: clinical testing
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Finnish congenital nephrotic syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002087098.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome. | Wang F | Pediatric nephrology (Berlin, Germany) | 2017 | PMID: 28204945 |
Genotype-phenotype correlations in non-Finnish congenital nephrotic syndrome. | Machuca E | Journal of the American Society of Nephrology : JASN | 2010 | PMID: 20507940 |
Neutropenia in congenital nephrotic syndrome of the Finnish type: role of urinary ceruloplasmin loss. | Ulinski T | Blood | 2009 | PMID: 19423745 |
Nephrin TRAP mice lack slit diaphragms and show fibrotic glomeruli and cystic tubular lesions. | Rantanen M | Journal of the American Society of Nephrology : JASN | 2002 | PMID: 12039988 |
Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration. | Koziell A | Human molecular genetics | 2002 | PMID: 11854170 |
Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome. | Beltcheva O | Human mutation | 2001 | PMID: 11317351 |
Text-mined citations for rs749341977 ...
HelpRecord last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.