ClinVar Genomic variation as it relates to human health
NM_004646.4(NPHS1):c.515_517del (p.Thr172del)
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.
Pathogenic(5); Likely pathogenic(3); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004646.4(NPHS1):c.515_517del (p.Thr172del)
Variation ID: 56509 Accession: VCV000056509.18
- Type and length
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Deletion, 3 bp
- Location
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Cytogenetic: 19q13.12 19: 35850970-35850972 (GRCh38) [ NCBI UCSC ] 19: 36341872-36341874 (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 Apr 6, 2024 Mar 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004646.4:c.515_517del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004637.1:p.Thr172del inframe deletion NM_004646.3:c.515_517delCCA NC_000019.10:g.35850972_35850974del NC_000019.9:g.36341874_36341876del NG_013356.2:g.23316_23318del NG_051206.1:g.4338_4340del LRG_693:g.23316_23318del LRG_693t1:c.515_517del LRG_693p1:p.Thr172del - Protein change
- T172del
- Other names
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- Canonical SPDI
- NC_000019.10:35850969:TGGTG:TG
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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.
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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
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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 |
1620 | 1797 |
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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Conflicting interpretations of pathogenicity (9) |
criteria provided, conflicting classifications
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Mar 26, 2024 | RCV000049922.17 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 20, 2023 | RCV001268096.5 | |
Likely pathogenic (1) |
no assertion criteria provided
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Nov 10, 2017 | RCV001849306.1 |
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. |
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Likely pathogenic
(Dec 07, 2017)
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criteria provided, single submitter
Method: clinical testing
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Finnish congenital nephrotic syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV000680319.1
First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018 |
Sex: male
Tissue: blood
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Pathogenic
(May 28, 2019)
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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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Mendelics
Accession: SCV001141052.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Pathogenic
(Sep 19, 2019)
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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: SCV001362147.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: NPHS1 c.515_517delCCA (p.Thr172del) results in an in-frame deletion that is predicted to remove a threonine residue from the second immunoglobulin-like domain (IPR013162) of … (more)
Variant summary: NPHS1 c.515_517delCCA (p.Thr172del) results in an in-frame deletion that is predicted to remove a threonine residue from the second immunoglobulin-like domain (IPR013162) of the encoded protein. The variant allele was found at a frequency of 8e-06 in 251116 control chromosomes (gnomAD). c.515_517delCCA has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Nephrotic Syndrome, Type 1 (e.g. Buscher_2010, Machuca_2010). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446749.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Prelingual sensorineural hearing impairment (present) , Thickened nuchal skin fold (present) , Delayed speech and language development (present) , Seizure (present) , Decreased circulating antibody … (more)
Prelingual sensorineural hearing impairment (present) , Thickened nuchal skin fold (present) , Delayed speech and language development (present) , Seizure (present) , Decreased circulating antibody level (present) , Relative macrocephaly (present) , Diffuse white matter abnormalities (present) , Congenital nephrotic syndrome (present) , Ureter duplex (present) (less)
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Likely pathogenic
(Jan 22, 2015)
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criteria provided, single submitter
Method: literature only
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Finnish congenital nephrotic syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000221070.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Sep 15, 2023)
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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: SCV004191408.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Uncertain significance
(Mar 16, 2020)
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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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Revvity Omics, Revvity
Accession: SCV003816065.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 20, 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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Invitae
Accession: SCV001592882.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This variant, c.515_517del, results in the deletion of 1 amino acid(s) of the NPHS1 protein (p.Thr172del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.515_517del, results in the deletion of 1 amino acid(s) of the NPHS1 protein (p.Thr172del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs386833947, gnomAD 0.006%). This variant has been observed in individual(s) with congential nephrotic syndrome (PMID: 9915943, 20507940, 20798252, 26560236). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.515delCCA. ClinVar contains an entry for this variant (Variation ID: 56509). For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Mar 26, 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:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806555.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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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: SCV000082331.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013
Comment:
FinDis database variant: 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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Pathogenic
(Jul 10, 2020)
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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: SCV002087109.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Likely pathogenic
(Nov 10, 2017)
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no assertion criteria provided
Method: literature only
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Nephrotic syndrome
Affected status: yes
Allele origin:
germline
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Yale Center for Mendelian Genomics, Yale University
Study: Yale Center for Mendelian Genomics
Accession: SCV002106813.1 First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 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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Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome. | Warejko JK | Clinical journal of the American Society of Nephrology : CJASN | 2018 | PMID: 29127259 |
NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described. | Guaragna MS | Nephrology (Carlton, Vic.) | 2016 | PMID: 26560236 |
A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families. | Al-Hamed MH | Journal of human genetics | 2013 | PMID: 23595123 |
Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. | Santín S | Clinical journal of the American Society of Nephrology : CJASN | 2011 | PMID: 21415313 |
Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. | Büscher AK | Clinical journal of the American Society of Nephrology : CJASN | 2010 | PMID: 20798252 |
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 |
Genetic forms of nephrotic syndrome: a single-center experience in Brussels. | Ismaili K | Pediatric nephrology (Berlin, Germany) | 2009 | PMID: 18709391 |
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 |
Structure of the gene for congenital nephrotic syndrome of the finnish type (NPHS1) and characterization of mutations. | Lenkkeri U | American journal of human genetics | 1999 | PMID: 9915943 |
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Text-mined citations for rs386833947 ...
HelpRecord last updated Apr 20, 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.