VCV000978405.4 - ClinVar

NM_001349338.3(FOXP1):c.1321_1324del (p.Asp441fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001349338.3(FOXP1):c.1321_1324del (p.Asp441fs)

Variation ID: 978405 Accession: VCV000978405.4

Type and length

Deletion, 4 bp

Location

Cytogenetic: 3p13 3: 70977852-70977855 (GRCh38) [ NCBI UCSC ] 3: 71027003-71027006 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Sep 27, 2020	Feb 28, 2024	Jul 2, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_001349338.3:c.1321_1324del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001336267.1:p.Asp441fs	frameshift
NM_001244808.3:c.1321_1324del	NP_001231737.1:p.Asp441fs	frameshift
NM_001244810.2:c.1321_1324del	NP_001231739.1:p.Asp441fs	frameshift
NM_001244812.3:c.1093_1096del	NP_001231741.1:p.Asp365fs	frameshift
NM_001244813.3:c.1021_1024del	NP_001231742.1:p.Asp341fs	frameshift
NM_001244814.3:c.1321_1324del	NP_001231743.1:p.Asp441fs	frameshift
NM_001244815.2:c.1021_1024del	NP_001231744.2:p.Asp341fs	frameshift
NM_001244816.2:c.1321_1324del	NP_001231745.1:p.Asp441fs	frameshift
NM_001349337.2:c.1018_1021del	NP_001336266.2:p.Asp340fs	frameshift
NM_001349340.3:c.1321_1324del	NP_001336269.1:p.Asp441fs	frameshift
NM_001349341.3:c.1318_1321del	NP_001336270.1:p.Asp440fs	frameshift
NM_001349342.3:c.1021_1024del	NP_001336271.1:p.Asp341fs	frameshift
NM_001349343.3:c.1018_1021del	NP_001336272.1:p.Asp340fs	frameshift
NM_001349344.3:c.1018_1021del	NP_001336273.1:p.Asp340fs	frameshift
NM_001370548.1:c.1021_1024del	NP_001357477.1:p.Asp341fs	frameshift
NM_032682.6:c.1321_1324del	NP_116071.2:p.Asp441fs	frameshift
NR_146142.3:n.1837_1840del		non-coding transcript variant
NR_146143.3:n.1834_1837del		non-coding transcript variant
NC_000003.12:g.70977854_70977857del
NC_000003.11:g.71027005_71027008del
NG_028243.1:g.611135_611138del

... more HGVS ... less HGVS

Protein change

D340fs, D341fs, D365fs, D440fs, D441fs

Other names

Canonical SPDI

NC_000003.12:70977851:TGTCTG:TG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
FOXP1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	829	907

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Rare genetic intellectual disability	Likely pathogenic (1)	no assertion criteria provided	-	RCV001257016.2
not provided	Pathogenic (1)	criteria provided, single submitter	Jul 2, 2020	RCV001385421.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jul 02, 2020)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001585258.3 First in ClinVar: May 10, 2021 Last updated: Feb 28, 2024	Publications: PubMed (1) PubMed: 28735298 Comment: This sequence change creates a premature translational stop signal (p.Asp441Asnfs32) in the FOXP1 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Asp441Asnfs32) in the FOXP1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FOXP1-related conditions. Loss-of-function variants in FOXP1 are known to be pathogenic (PMID: 28735298). For these reasons, this variant has been classified as Pathogenic. (less)
Likely pathogenic (-)	no assertion criteria provided Method: clinical testing	Rare genetic intellectual disability Affected status: yes Allele origin: de novo	Service de Génétique Moléculaire, Hôpital Robert Debré Accession: SCV001433572.1 First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020

Comment:

This sequence change creates a premature translational stop signal (p.Asp441Asnfs*32) in the FOXP1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FOXP1-related conditions. Loss-of-function variants in FOXP1 are known to be pathogenic (PMID: 28735298). For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
FOXP1-related intellectual disability syndrome: a recognisable entity.	Meerschaut I	Journal of medical genetics	2017	PMID: 28735298

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001349338.3(FOXP1):c.1321_1324del (p.Asp441fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...