NM_015102.5(NPHP4):c.3718T>C (p.Cys1240Arg) AND Nephronophthisis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 13, 2019
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:: RCV001212086.8

Allele description [Variation Report for NM_015102.5(NPHP4):c.3718T>C (p.Cys1240Arg)]

NM_015102.5(NPHP4):c.3718T>C (p.Cys1240Arg)

Gene:

NPHP4:nephrocystin 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.31

Genomic location:

Preferred name:

NM_015102.5(NPHP4):c.3718T>C (p.Cys1240Arg)

HGVS:

NC_000001.11:g.5865200A>G
NG_011724.2:g.132272T>C
NM_001291593.2:c.2179T>C
NM_001291594.2:c.2182T>C
NM_015102.5:c.3718T>CMANE SELECT
NP_001278522.1:p.Cys727Arg
NP_001278523.1:p.Cys728Arg
NP_055917.1:p.Cys1240Arg
NC_000001.10:g.5925260A>G
NM_015102.3:c.3718T>C
NM_015102.4:c.3718T>C
NR_111987.2:n.4485T>C

Protein change:

C1240R

Links:

dbSNP: rs1028037857

NCBI 1000 Genomes Browser:

rs1028037857

Molecular consequence:

NM_001291593.2:c.2179T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001291594.2:c.2182T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015102.5:c.3718T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_111987.2:n.4485T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Nephronophthisis
Synonyms:: juvenile nephronophthisis
Identifiers:: MONDO: MONDO:0019005; MedGen: C0687120; OMIM: PS256100; Human Phenotype Ontology: HP:0000090

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001383660	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 13, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001383660

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 13, 2019)

germline

clinical testing

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001383660.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NPHP4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 1240 of the NPHP4 protein (p.Cys1240Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine.

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

Last Updated: Sep 29, 2024

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