U.S. flag

An official website of the United States government

NM_024426.6(WT1):c.218A>T (p.Gln73Leu) AND Nephrotic syndrome, type 4

Germline classification:
Likely benign (1 submission)
Last evaluated:
May 6, 2021
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:
RCV004787897.1

Allele description [Variation Report for NM_024426.6(WT1):c.218A>T (p.Gln73Leu)]

NM_024426.6(WT1):c.218A>T (p.Gln73Leu)

Genes:
WT1:WT1 transcription factor [Gene - OMIM - HGNC]
LOC107982234:WT1/WT1-AS bi-directional promoter region [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
11p13
Genomic location:
Preferred name:
NM_024426.6(WT1):c.218A>T (p.Gln73Leu)
HGVS:
  • NC_000011.10:g.32435143T>A
  • NG_009272.1:g.5399A>T
  • NG_050766.1:g.4396T>A
  • NM_000378.6:c.218A>T
  • NM_024424.5:c.218A>T
  • NM_024426.6:c.218A>TMANE SELECT
  • NP_000369.4:p.Gln73Leu
  • NP_077742.3:p.Gln73Leu
  • NP_077744.4:p.Gln73Leu
  • LRG_525t1:c.203A>T
  • LRG_525:g.5399A>T
  • NC_000011.9:g.32456689T>A
  • NM_024426.3:c.203A>T
  • NM_024426.4:c.203A>T
  • NR_160306.1:n.397A>T
Protein change:
Q73L
Links:
dbSNP: rs1036899554
NCBI 1000 Genomes Browser:
rs1036899554
Molecular consequence:
  • NM_000378.6:c.218A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024424.5:c.218A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_024426.6:c.218A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_160306.1:n.397A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Nephrotic syndrome, type 4 (NPHS4)
Synonyms:
Familial mesangial sclerosis; Nephrotic syndrome, early onset with diffuse mesangial sclerosis
Identifiers:
MONDO: MONDO:0009733; MedGen: C3151568; Orphanet: 656; OMIM: 256370

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005398542Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely benign
(May 6, 2021) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Frequency and timing of loss of imprinting at 11p13 and 11p15 in Wilms' tumor development.

Brown KW, Power F, Moore B, Charles AK, Malik KT.

Mol Cancer Res. 2008 Jul;6(7):1114-23. doi: 10.1158/1541-7786.MCR-08-0002.

PubMed [citation]
PMID:
18644976

A novel missense mutation of Wilms' Tumor 1 causes autosomal dominant FSGS.

Hall G, Gbadegesin RA, Lavin P, Wu G, Liu Y, Oh EC, Wang L, Spurney RF, Eckel J, Lindsey T, Homstad A, Malone AF, Phelan PJ, Shaw A, Howell DN, Conlon PJ, Katsanis N, Winn MP.

J Am Soc Nephrol. 2015 Apr;26(4):831-43. doi: 10.1681/ASN.2013101053. Epub 2014 Aug 21.

PubMed [citation]
PMID:
25145932
PMCID:
PMC4378093
See all PubMed Citations (4)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005398542.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely benign. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with WT1-related disease. Variants predicted to undergo nonsense-mediated decay, and truncating variants lacking the zinc-finger motifs, have been reported with a loss of function (LOF) and dominant negative (DN) mechanism, respectively. Missense variants are have been functionally proven to have a LOF effect, however, more investigation is required to exclude if DN is also occurring (Decipher, GeneReviews, PMID: 26090994, PMID: 25145932). (I) 0107 - This gene is associated with autosomal dominant disease. The diseases were previously regarded as different syndromes, but are now considered part of a phenotypic continuum (GeneReviews). (I) 0113 - This gene is known to be imprinted (NCBI). Loss of imprinting in wilms tumours has been reported (PMID: 18644976). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamine to leucine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (3 heterozygotes, 0 homozygotes), but has been misannotated as p.(Gln73Leu). (SP) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0808 - Previous reports of pathogenicity for this variant are conflicting. This variant has been reported as likely benign and as a VUS (LOVD, ClinVar). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: May 16, 2025