ClinVar Genomic variation as it relates to human health
NM_004646.4(NPHS1):c.1715G>A (p.Ser572Asn)
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.1715G>A (p.Ser572Asn)
Variation ID: 56447 Accession: VCV000056447.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19q13.12 19: 35845711 (GRCh38) [ NCBI UCSC ] 19: 36336613 (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 Jul 24, 2013 Feb 14, 2024 Feb 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004646.4:c.1715G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004637.1:p.Ser572Asn missense NC_000019.10:g.35845711C>T NC_000019.9:g.36336613C>T NG_013356.2:g.28577G>A LRG_693:g.28577G>A LRG_693t1:c.1715G>A LRG_693p1:p.Ser572Asn O60500:p.Ser572Asn - Protein change
- S572N
- Other names
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- Canonical SPDI
- NC_000019.10:35845710:C:T
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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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
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 | ||
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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
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. |
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NPHS1 | - | - |
GRCh38 GRCh37 |
1670 | 1853 |
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
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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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Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 11, 2022 | RCV000049860.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2023 | RCV000487117.8 |
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. |
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Likely pathogenic
(Mar 11, 2022)
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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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Fulgent Genetics, Fulgent Genetics
Accession: SCV002813939.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Feb 01, 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: SCV001233250.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser572 amino acid residue in NPHS1. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser572 amino acid residue in NPHS1. Other variant(s) that disrupt this residue have been observed in individuals with NPHS1-related conditions (PMID: 18503012, 26248470), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 56447). This missense change has been observed in individual(s) with congenital nephrotic syndrome (PMID: 15906409, 20172850, 29474669). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs386833889, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 572 of the NPHS1 protein (p.Ser572Asn). (less)
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Likely pathogenic
(Feb 09, 2017)
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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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Counsyl
Accession: SCV000789515.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013 |
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Pathogenic
(Feb 24, 2020)
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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: SCV000568764.5
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious … (more)
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15906409, 20172850, 27019444, 20507940) (less)
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probable-pathogenic
(-)
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no assertion criteria provided
Method: not provided
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Finnish congenital nephrotic syndrome
Affected status: not provided
Allele origin:
not provided
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Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082269.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
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Comment:
Converted during submission to Likely pathogenic.
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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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Treatment and outcome of congenital nephrotic syndrome. | Bérody S | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2019 | PMID: 29474669 |
Dealing with the incidental finding of secondary variants by the example of SRNS patients undergoing targeted next-generation sequencing. | Weber S | Pediatric nephrology (Berlin, Germany) | 2016 | PMID: 26248470 |
Genotype-phenotype correlations in non-Finnish congenital nephrotic syndrome. | Machuca E | Journal of the American Society of Nephrology : JASN | 2010 | PMID: 20507940 |
Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS). | Schoeb DS | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2010 | PMID: 20172850 |
Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome. | Heeringa SF | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2008 | PMID: 18503012 |
Congenital nephrotic syndrome of Finnish type: detection of new nephrin mutations and prenatal diagnosis in an Italian family. | Gigante M | Prenatal diagnosis | 2005 | PMID: 15906409 |
Text-mined citations for rs386833889 ...
HelpRecord last updated Sep 29, 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.