NM_001379286.1(ZNF423):c.3364G>A (p.Asp1122Asn) AND Nephronophthisis 14

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 9, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001372081.8

Allele description [Variation Report for NM_001379286.1(ZNF423):c.3364G>A (p.Asp1122Asn)]

NM_001379286.1(ZNF423):c.3364G>A (p.Asp1122Asn)

Gene:

ZNF423:zinc finger protein 423 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_001379286.1(ZNF423):c.3364G>A (p.Asp1122Asn)

HGVS:

NC_000016.10:g.49635812C>T
NG_032972.2:g.227108G>A
NM_001271620.2:c.3160G>A
NM_001330533.2:c.2989G>A
NM_001379286.1:c.3364G>AMANE SELECT
NM_015069.2:c.3340G>A
NM_015069.5:c.3340G>A
NP_001258549.1:p.Asp1054Asn
NP_001317462.1:p.Asp997Asn
NP_001366215.1:p.Asp1122Asn
NP_055884.2:p.Asp1114Asn
NC_000016.9:g.49669723C>T
NM_015069.4:c.3340G>A

Protein change:

D1054N

Links:

dbSNP: rs771960577

NCBI 1000 Genomes Browser:

rs771960577

Molecular consequence:

NM_001271620.2:c.3160G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330533.2:c.2989G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379286.1:c.3364G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015069.5:c.3340G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Nephronophthisis 14 (NPHP14)
Identifiers:: MONDO: MONDO:0013916; MedGen: C3539071; Orphanet: 2318; OMIM: 614844

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001568676	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002790691	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 30, 2021)	unknown	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

SCV001568676

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 9, 2022)

germline

clinical testing

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

SCV002790691

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 30, 2021)

unknown

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
not provided	unknown	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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001568676.4

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1062375). This variant has not been reported in the literature in individuals affected with ZNF423-related conditions. This variant is present in population databases (rs771960577, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1114 of the ZNF423 protein (p.Asp1114Asn).

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002790691.1

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

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

Last Updated: Nov 24, 2024

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