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NM_004646.4(NPHS1):c.1379G>A (p.Arg460Gln) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 2, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001388275.12

Allele description [Variation Report for NM_004646.4(NPHS1):c.1379G>A (p.Arg460Gln)]

NM_004646.4(NPHS1):c.1379G>A (p.Arg460Gln)

Gene:
NPHS1:NPHS1 adhesion molecule, nephrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.12
Genomic location:
Preferred name:
NM_004646.4(NPHS1):c.1379G>A (p.Arg460Gln)
HGVS:
  • NC_000019.10:g.35848102C>T
  • NG_013356.2:g.26186G>A
  • NG_051206.1:g.1468C>T
  • NM_004646.4:c.1379G>AMANE SELECT
  • NP_004637.1:p.Arg460Gln
  • NP_004637.1:p.Arg460Gln
  • LRG_693t1:c.1379G>A
  • LRG_693:g.26186G>A
  • LRG_693p1:p.Arg460Gln
  • NC_000019.9:g.36339004C>T
  • NM_004646.3:c.1379G>A
  • O60500:p.Arg460Gln
Protein change:
R460Q
Links:
UniProtKB: O60500#VAR_064209; dbSNP: rs386833880
NCBI 1000 Genomes Browser:
rs386833880
Molecular consequence:
  • NM_004646.4:c.1379G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001589205Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 2, 2024)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004145519CeGaT Center for Human Genetics Tuebingen
criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)
Pathogenic
(Nov 1, 2022)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Two Korean infants with genetically confirmed congenital nephrotic syndrome of Finnish type.

Lee BH, Ahn YH, Choi HJ, Kang HK, Kim SD, Cho BS, Moon KC, Ha IS, Cheong HI, Choi Y.

J Korean Med Sci. 2009 Jan;24 Suppl:S210-4. doi: 10.3346/jkms.2009.24.S1.S210. Epub 2009 Jan 28.

PubMed [citation]
PMID:
19194555
PMCID:
PMC2633182

Novel mutations in steroid-resistant nephrotic syndrome diagnosed in Tunisian children.

Mbarek IB, Abroug S, Omezzine A, Pawtowski A, Gubler MC, Bouslama A, Harbi A, Antignac C.

Pediatr Nephrol. 2011 Feb;26(2):241-9. doi: 10.1007/s00467-010-1694-8. Epub 2010 Dec 2.

PubMed [citation]
PMID:
21125408
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001589205.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 460 of the NPHS1 protein (p.Arg460Gln). This variant is present in population databases (rs386833880, gnomAD 0.003%). This missense change has been observed in individual(s) with nephrotic syndrome (PMID: 19194555, 21125408, 21415313, 30655312). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56438). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From CeGaT Center for Human Genetics Tuebingen, SCV004145519.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

NPHS1: PM3:Very Strong, PM2, PS4:Moderate, PS3:Supporting, BP4

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Jul 15, 2024