NM_012186.3(FOXE3):c.335C>A (p.Pro112Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 14, 2023
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:: RCV003802238.1

Allele description [Variation Report for NM_012186.3(FOXE3):c.335C>A (p.Pro112Gln)]

NM_012186.3(FOXE3):c.335C>A (p.Pro112Gln)

Genes:

FOXE3:forkhead box E3 [Gene - OMIM - HGNC]
LINC01389:long intergenic non-protein coding RNA 1389 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p33

Genomic location:

Preferred name:

NM_012186.3(FOXE3):c.335C>A (p.Pro112Gln)

HGVS:

NC_000001.11:g.47416650C>A
NG_016192.1:g.5579C>A
NM_012186.3:c.335C>AMANE SELECT
NP_036318.1:p.Pro112Gln
NC_000001.10:g.47882322C>A

Protein change:

P112Q

Molecular consequence:

NM_012186.3:c.335C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital primary aphakia
Synonyms:: ANTERIOR SEGMENT DYSGENESIS 2; Anterior segment dysgenesis 2, multiple subtypes
Identifiers:: MONDO: MONDO:0012456; MedGen: C1853230; Orphanet: 83461; OMIM: 610256

Name:: Anterior segment dysgenesis
Synonyms:: Ocular anterior segment dysgenesis
Identifiers:: MONDO: MONDO:0019503; MedGen: C1862839; OMIM: PS107250; Human Phenotype Ontology: HP:0007700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004608826	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 14, 2023)	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

SCV004608826

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 14, 2023)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004608826.1

#	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 proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 112 of the FOXE3 protein (p.Pro112Gln). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FOXE3 protein function. This variant has not been reported in the literature in individuals affected with FOXE3-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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: Apr 15, 2024

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