NM_004646.4(NPHS1):c.728C>T (p.Pro243Leu) AND Finnish congenital nephrotic syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 22, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002250775.1

Allele description [Variation Report for NM_004646.4(NPHS1):c.728C>T (p.Pro243Leu)]

NM_004646.4(NPHS1):c.728C>T (p.Pro243Leu)

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.728C>T (p.Pro243Leu)

HGVS:

NC_000019.10:g.35849348G>A
NG_013356.2:g.24940C>T
NG_051206.1:g.2714G>A
NM_004646.4:c.728C>TMANE SELECT
NP_004637.1:p.Pro243Leu
LRG_693t1:c.728C>T
LRG_693:g.24940C>T
NC_000019.9:g.36340250G>A
NM_004646.3:c.728C>T

Protein change:

P243L

Links:

dbSNP: rs919999972

NCBI 1000 Genomes Browser:

rs919999972

Molecular consequence:

NM_004646.4:c.728C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Finnish congenital nephrotic syndrome (NPHS1)
Synonyms:: NEPHROTIC SYNDROME, TYPE 1; Nephrosis 1, congenital, Finnish type; Congenital nephrotic syndrome 1
Identifiers:: MONDO: MONDO:0009732; MedGen: C0403399; Orphanet: 839; OMIM: 256300

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Mus musculus mitochondrial ribosomal protein S17 (Mrps17), transcript variant 5,...
Mus musculus mitochondrial ribosomal protein S17 (Mrps17), transcript variant 5, mRNA
gi|1255287549|ref|NM_001356957.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002521682	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28921387, 30655312, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521682

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 22, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Analysis of 24 genes reveals a monogenic cause in 11.1% of cases with steroid-resistant nephrotic syndrome at a single center.

Tan W, Lovric S, Ashraf S, Rao J, Schapiro D, Airik M, Shril S, Gee HY, Baum M, Daouk G, Ferguson MA, Rodig N, Somers MJG, Stein DR, Vivante A, Warejko JK, Widmeier E, Hildebrandt F.

Pediatr Nephrol. 2018 Feb;33(2):305-314. doi: 10.1007/s00467-017-3801-6. Epub 2017 Sep 18.

PubMed [citation]

PMID:: 28921387
PMCID:: PMC5771840

Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients.

Mann N, Braun DA, Amann K, Tan W, Shril S, Connaughton DM, Nakayama M, Schneider R, Kitzler TM, van der Ven AT, Chen J, Ityel H, Vivante A, Majmundar AJ, Daga A, Warejko JK, Lovric S, Ashraf S, Jobst-Schwan T, Widmeier E, Hugo H, Mane SM, et al.

J Am Soc Nephrol. 2019 Feb;30(2):201-215. doi: 10.1681/ASN.2018060575. Epub 2019 Jan 17.

PubMed [citation]

PMID:: 30655312
PMCID:: PMC6362619

See all PubMed Citations (3)

Details of each submission

From 3billion, SCV002521682.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Same nucleotide change resulting in same amino acid change has been previously reported to be associated with NPHS1 related disorder (PMID: 28921387, 30655312). The variant has been observed in at least two similarly affected unrelated individuals (PMID:28921387, 30655312). In addition, It has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID:28921387, 30655312). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Dec 24, 2023

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