NM_001453.3(FOXC1):c.405C>A (p.Cys135Ter) AND Axenfeld-Rieger syndrome type 3

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 14, 2019
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:: RCV001063142.8

Allele description [Variation Report for NM_001453.3(FOXC1):c.405C>A (p.Cys135Ter)]

NM_001453.3(FOXC1):c.405C>A (p.Cys135Ter)

Gene:

FOXC1:forkhead box C1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p25.3

Genomic location:

Preferred name:

NM_001453.3(FOXC1):c.405C>A (p.Cys135Ter)

HGVS:

NC_000006.12:g.1610850C>A
NG_009368.1:g.5405C>A
NM_001453.3:c.405C>AMANE SELECT
NP_001444.2:p.Cys135Ter
LRG_1245t1:c.405C>A
LRG_1245:g.5405C>A
LRG_1245p1:p.Cys135Ter
NC_000006.11:g.1611085C>A
NM_001453.2:c.405C>A

Protein change:

C135*

Links:

dbSNP: rs2230096

NCBI 1000 Genomes Browser:

rs2230096

Molecular consequence:

NM_001453.3:c.405C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Axenfeld-Rieger syndrome type 3 (RIEG3)
Synonyms:: Axenfeld-rieger anomaly with or without cardiac defects and/or sensorineural hearing loss; Rieger syndrome type 3; Anterior chamber cleavage syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011233; MedGen: C2678503; Orphanet: 782; OMIM: 602482

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001227976	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 14, 2019)	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

SCV001227976

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 14, 2019)

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, SCV001227976.5

#	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 results in a premature translational stop signal in the FOXC1 gene (p.Cys135*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 419 amino acids of the FOXC1 protein. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the FOXC1 protein. Other variant(s) that disrupt this region (p.Ser320Argfs*81) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with FOXC1-related conditions.

#	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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