NM_012193.4(FZD4):c.456C>G (p.Asn152Lys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 4, 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:: RCV003062438.3

Allele description [Variation Report for NM_012193.4(FZD4):c.456C>G (p.Asn152Lys)]

NM_012193.4(FZD4):c.456C>G (p.Asn152Lys)

Genes:

FZD4:frizzled class receptor 4 [Gene - OMIM - HGNC]
PRSS23:serine protease 23 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q14.2

Genomic location:

Preferred name:

NM_012193.4(FZD4):c.456C>G (p.Asn152Lys)

HGVS:

NC_000011.10:g.86952300G>C
NG_011752.2:g.8095C>G
NM_012193.4:c.456C>GMANE SELECT
NP_036325.2:p.Asn152Lys
NC_000011.9:g.86663342G>C
NG_011752.1:g.8092C>G
NR_120591.3:n.1663G>C
NR_120592.2:n.1412G>C

Protein change:

N152K

Molecular consequence:

NM_012193.4:c.456C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_120591.3:n.1663G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_120592.2:n.1412G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003440452	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 4, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26244290, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003440452

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 4, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular Characterization of FZD4, LRP5, and TSPAN12 in Familial Exudative Vitreoretinopathy.

Seo SH, Yu YS, Park SW, Kim JH, Kim HK, Cho SI, Park H, Lee SJ, Seong MW, Park SS, Kim JY.

Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5143-51. doi: 10.1167/iovs.14-15680.

PubMed [citation]

PMID:: 26244290

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, SCV003440452.2

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

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FZD4 protein function. This missense change has been observed in individual(s) with exudative vitreoretinopathy (PMID: 26244290). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 152 of the FZD4 protein (p.Asn152Lys).

#	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

ClinVar

Relating variation to medicine