NM_001012426.2(FOXP4):c.1540G>A (p.Ala514Thr) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 14, 2021
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:: RCV001969335.7

Allele description [Variation Report for NM_001012426.2(FOXP4):c.1540G>A (p.Ala514Thr)]

NM_001012426.2(FOXP4):c.1540G>A (p.Ala514Thr)

Gene:

FOXP4:forkhead box P4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_001012426.2(FOXP4):c.1540G>A (p.Ala514Thr)

HGVS:

NC_000006.12:g.41594873G>A
NM_001012426.2:c.1540G>AMANE SELECT
NM_001012427.2:c.1534G>A
NM_138457.3:c.1501G>A
NP_001012426.1:p.Ala514Thr
NP_001012427.1:p.Ala512Thr
NP_612466.1:p.Ala501Thr
NC_000006.11:g.41562611G>A
NM_001012426.1:c.1540G>A

Protein change:

A501T

Links:

dbSNP: rs2127404974

NCBI 1000 Genomes Browser:

rs2127404974

Molecular consequence:

NM_001012426.2:c.1540G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001012427.2:c.1534G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_138457.3:c.1501G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002251871	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 14, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004031318	Molecular Genetics laboratory, Necker Hospital	no assertion criteria provided	Pathogenic (Apr 12, 2021)	de novo	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002251871

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 14, 2021)

germline

clinical testing

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

SCV004031318

Molecular Genetics laboratory, Necker Hospital

no assertion criteria provided

Pathogenic
(Apr 12, 2021)

de novo

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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, SCV002251871.3

#	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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of FOXP4-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 514 of the FOXP4 protein (p.Ala514Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.

#	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 Molecular Genetics laboratory, Necker Hospital, SCV004031318.1

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

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

Last Updated: Sep 29, 2024

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