NM_015102.5(NPHP4):c.3335G>A (p.Gly1112Asp) AND Nephronophthisis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 18, 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:: RCV001955704.3

Allele description [Variation Report for NM_015102.5(NPHP4):c.3335G>A (p.Gly1112Asp)]

NM_015102.5(NPHP4):c.3335G>A (p.Gly1112Asp)

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.3335G>A (p.Gly1112Asp)

HGVS:

NC_000001.11:g.5867877C>T
NG_011724.2:g.129595G>A
NM_001291593.2:c.1796G>A
NM_001291594.2:c.1799G>A
NM_015102.5:c.3335G>AMANE SELECT
NP_001278522.1:p.Gly599Asp
NP_001278523.1:p.Gly600Asp
NP_055917.1:p.Gly1112Asp
NC_000001.10:g.5927937C>T
NM_015102.3:c.3335G>A
NR_111987.2:n.4102G>A

Protein change:

G1112D

Links:

dbSNP: rs755637892

NCBI 1000 Genomes Browser:

rs755637892

Molecular consequence:

NM_001291593.2:c.1796G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291594.2:c.1799G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015102.5:c.3335G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_111987.2:n.4102G>A - 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
SCV002220090	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 18, 2021)	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

SCV002220090

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 18, 2021)

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, SCV002220090.2

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

Description

This sequence change replaces glycine with aspartic acid at codon 1112 of the NPHP4 protein (p.Gly1112Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs755637892, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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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