NM_001349338.3(FOXP1):c.116G>C (p.Gly39Ala) AND Intellectual disability-severe speech delay-mild dysmorphism syndrome

Germline classification:: Uncertain significance (1 submission)
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:: RCV002510725.3

Allele description [Variation Report for NM_001349338.3(FOXP1):c.116G>C (p.Gly39Ala)]

NM_001349338.3(FOXP1):c.116G>C (p.Gly39Ala)

Gene:

FOXP1:forkhead box P1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p13

Genomic location:

Preferred name:

NM_001349338.3(FOXP1):c.116G>C (p.Gly39Ala)

HGVS:

NC_000003.12:g.71198266C>G
NG_028243.1:g.390724G>C
NM_001012505.2:c.116G>C
NM_001244808.3:c.116G>C
NM_001244810.2:c.116G>C
NM_001244812.3:c.116G>C
NM_001244814.3:c.116G>C
NM_001244816.2:c.116G>C
NM_001349338.3:c.116G>CMANE SELECT
NM_001349339.1:c.116G>C
NM_001349340.3:c.116G>C
NM_001349341.3:c.116G>C
NM_032682.6:c.116G>C
NP_001012523.1:p.Gly39Ala
NP_001231737.1:p.Gly39Ala
NP_001231739.1:p.Gly39Ala
NP_001231741.1:p.Gly39Ala
NP_001231743.1:p.Gly39Ala
NP_001231745.1:p.Gly39Ala
NP_001336267.1:p.Gly39Ala
NP_001336268.1:p.Gly39Ala
NP_001336269.1:p.Gly39Ala
NP_001336270.1:p.Gly39Ala
NP_116071.2:p.Gly39Ala
NC_000003.11:g.71247417C>G
NM_032682.5:c.116G>C
NR_146142.3:n.720G>C
NR_146143.3:n.720G>C

Protein change:

G39A

Molecular consequence:

NM_001012505.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001244808.3:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001244810.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001244812.3:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001244814.3:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001244816.2:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349338.3:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349339.1:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349340.3:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349341.3:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_032682.6:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_146142.3:n.720G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146143.3:n.720G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Intellectual disability-severe speech delay-mild dysmorphism syndrome (IDDLA)
Synonyms:: Mental retardation with language impairment and autistic features
Identifiers:: MONDO: MONDO:0013352; MedGen: C4013764; Orphanet: 391372; OMIM: 613670

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002820268	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV002820268

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV002820268.1

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

Description

The missense variant p.G39A in FOXP1 (NM_032682.5) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.G39A variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a small physicochemical difference between glycine and alanine, which is not likely to impact secondary protein structure as these residues share similar properties. The p.G39A missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 39 of FOXP1 is conserved in all mammalian species. The nucleotide c.116 in FOXP1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance

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

Last Updated: Sep 16, 2024

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