NM_020401.4(NUP107):c.469G>T (p.Asp157Tyr) AND Nephrotic syndrome, type 11

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Sep 1, 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:: RCV000203505.3

Allele description [Variation Report for NM_020401.4(NUP107):c.469G>T (p.Asp157Tyr)]

NM_020401.4(NUP107):c.469G>T (p.Asp157Tyr)

Gene:

NUP107:nucleoporin 107 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q15

Genomic location:

Preferred name:

NM_020401.4(NUP107):c.469G>T (p.Asp157Tyr)

HGVS:

NC_000012.12:g.68696839G>T
NG_046600.2:g.14889G>T
NM_001330192.2:c.382G>T
NM_020401.4:c.469G>TMANE SELECT
NP_001317121.1:p.Asp128Tyr
NP_065134.1:p.Asp157Tyr
NC_000012.11:g.69090619G>T
P57740:p.Asp157Tyr

Protein change:

D128Y; ASP157TYR

Links:

UniProtKB: P57740#VAR_076358; OMIM: 607617.0004; dbSNP: rs864321633

NCBI 1000 Genomes Browser:

rs864321633

Molecular consequence:

NM_001330192.2:c.382G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_020401.4:c.469G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Nephrotic syndrome, type 11 (NPHS11)
Identifiers:: MONDO: MONDO:0014752; MedGen: C4225228; Orphanet: 656; OMIM: 616730

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000258613	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 2015)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002572847	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26411495, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000258613

OMIM

no assertion criteria provided

Pathogenic
(Oct 1, 2015)

germline

literature only

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

SCV002572847

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 1, 2022)

germline

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Biallelic Mutations in Nuclear Pore Complex Subunit NUP107 Cause Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome.

Miyake N, Tsukaguchi H, Koshimizu E, Shono A, Matsunaga S, Shiina M, Mimura Y, Imamura S, Hirose T, Okudela K, Nozu K, Akioka Y, Hattori M, Yoshikawa N, Kitamura A, Cheong HI, Kagami S, Yamashita M, Fujita A, Miyatake S, Tsurusaki Y, Nakashima M, et al.

Am J Hum Genet. 2015 Oct 1;97(4):555-66. doi: 10.1016/j.ajhg.2015.08.013. Epub 2015 Sep 24.

PubMed [citation]

PMID:: 26411495
PMCID:: PMC4596915

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000258613.2

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

Description

In 2 Korean sisters (family SRNS-12) with nephrotic syndrome type 11 (NPHS11; 616730), Miyake et al. (2015) identified compound heterozygous missense mutations in the NUP107 gene: a c.469G-T transversion (c.469-G-T, NM_020401.2), resulting in an asp157-to-tyr (D157Y) substitution, and D831A (607617.0001). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The D157Y mutation was not found in the Exome Variant Server, ExAC, or Japanese Human Genetic Variation databases, or in an in-house database of 575 Japanese exomes. In vitro functional expression studies showed that the D157Y mutation did not affect the binding to NUP133 (607613). The patients had slightly later onset of the disorder compared to other patients with NPHS11, and Miyake et al. (2015) postulated a genotype/phenotype correlation, since both alleles carried missense mutations.

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

From 3billion, SCV002572847.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. Same nucleotide change resulting in same amino acid change has been previously reported to be associated with NUP107-related disorder (ClinVar ID: VCV000219130 / PMID: 26411495). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 26411495). The variant 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: 26411495). 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: Sep 24, 2022

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