NM_004646.4(NPHS1):c.3250dup (p.Val1084fs) AND Nephrotic syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 28, 2018
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001328317.2

Allele description [Variation Report for NM_004646.4(NPHS1):c.3250dup (p.Val1084fs)]

NM_004646.4(NPHS1):c.3250dup (p.Val1084fs)

Gene:

NPHS1:NPHS1 adhesion molecule, nephrin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

19q13.12

Genomic location:

Preferred name:

NM_004646.4(NPHS1):c.3250dup (p.Val1084fs)

HGVS:

NC_000019.10:g.35831685dup
NG_013356.2:g.42609dup
NM_004646.4:c.3250dupMANE SELECT
NP_004637.1:p.Val1084fs
NP_004637.1:p.Val1084fs
LRG_693t1:c.3250dup
LRG_693:g.42609dup
LRG_693p1:p.Val1084fs
NC_000019.9:g.36322580_36322581insC
NC_000019.9:g.36322587dup
NM_004646.3:c.3250dup
NM_004646.3:c.3250dupG

Protein change:

V1084fs

Links:

OMIM: 602716.0004; dbSNP: rs386833935

Molecular consequence:

NM_004646.4:c.3250dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Nephrotic syndrome
Identifiers:: MONDO: MONDO:0005377; MedGen: C0027726; Human Phenotype Ontology: HP:0000100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001449376	Sydney Genome Diagnostics, Children's Hospital Westmead	no assertion criteria provided	Pathogenic (Aug 28, 2018)	unknown	clinical testing
SCV002106880	Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics	no assertion criteria provided	Likely pathogenic (Nov 10, 2017)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001449376

Sydney Genome Diagnostics, Children's Hospital Westmead

no assertion criteria provided

Pathogenic
(Aug 28, 2018)

unknown

clinical testing

SCV002106880

Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics

no assertion criteria provided

Likely pathogenic
(Nov 10, 2017)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome.

Warejko JK, Tan W, Daga A, Schapiro D, Lawson JA, Shril S, Lovric S, Ashraf S, Rao J, Hermle T, Jobst-Schwan T, Widmeier E, Majmundar AJ, Schneider R, Gee HY, Schmidt JM, Vivante A, van der Ven AT, Ityel H, Chen J, Sadowski CE, Kohl S, et al.

Clin J Am Soc Nephrol. 2018 Jan 6;13(1):53-62. doi: 10.2215/CJN.04120417. Epub 2017 Nov 10.

PubMed [citation]

PMID:: 29127259
PMCID:: PMC5753307

Details of each submission

From Sydney Genome Diagnostics, Children's Hospital Westmead, SCV001449376.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

This patient is also heterozygous for a known pathogenic variant, c.3250dup, in the NPHS1 gene. This frameshifting variant (dbSNP: rs386833936) is predicted to create a premature stop codon 11 positions downstream (p.Val1084Glyfs*12), and may result in a null allele due to nonsense-mediated mRNA decay. This variant is considered to be pathogenic, and has been previously reported in patients with congenital nephrotic syndrome of Finnish type in the literature (Kestila et al 1998 Mol Cell 1:575-582; Lenkkeri et al 1999 Am J Hum Genet 64:51-61; Lee et al 2009 J Korean Med Sci 24:S210-S214).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Yale Center for Mendelian Genomics, Yale University - Yale Center for Mendelian Genomics, SCV002106880.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 3, 2026

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