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NM_012193.4(FZD4):c.758G>A (p.Arg253His) AND not provided

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 12, 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:
RCV001366843.6

Allele description

NM_012193.4(FZD4):c.758G>A (p.Arg253His)

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.758G>A (p.Arg253His)
HGVS:
  • NC_000011.10:g.86951998C>T
  • NG_011752.1:g.8394G>A
  • NM_012193.4:c.758G>AMANE SELECT
  • NP_036325.2:p.Arg253His
  • NC_000011.9:g.86663040C>T
  • NR_120591.3:n.1361C>T
  • NR_120592.2:n.1110C>T
Protein change:
R253H
Links:
dbSNP: rs761845677
NCBI 1000 Genomes Browser:
rs761845677
Molecular consequence:
  • NM_012193.4:c.758G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_120591.3:n.1361C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_120592.2:n.1110C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001563160Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 12, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel frizzled-4 gene mutations in chinese patients with familial exudative vitreoretinopathy.

Jia LY, Li XX, Yu WZ, Zeng WT, Liang C.

Arch Ophthalmol. 2010 Oct;128(10):1341-9. doi: 10.1001/archophthalmol.2010.240.

PubMed [citation]
PMID:
20938005

Spectrum of Variants in 389 Chinese Probands With Familial Exudative Vitreoretinopathy.

Li JK, Li Y, Zhang X, Chen CL, Rao YQ, Fei P, Zhang Q, Zhao P, Li J.

Invest Ophthalmol Vis Sci. 2018 Nov 1;59(13):5368-5381. doi: 10.1167/iovs.17-23541.

PubMed [citation]
PMID:
30452590
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001563160.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

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. This variant disrupts the p.Arg253 amino acid residue in FZD4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20938005, 30452590, 31987760). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1057788). This variant has not been reported in the literature in individuals affected with FZD4-related conditions. This variant is present in population databases (rs761845677, gnomAD 0.05%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 253 of the FZD4 protein (p.Arg253His).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 14, 2024