VCV003376315.1 - ClinVar

NM_001349338.3(FOXP1):c.1547del (p.Asn516fs)

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.

(1)

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.

Likely 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.1547del (p.Asn516fs)

Variation ID: 3376315 Accession: VCV003376315.1

Type and length

Deletion, 1 bp

Location

Cytogenetic: 3p13 3: 70972660 (GRCh38) [ NCBI UCSC ] 3: 71021811 (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	Nov 19, 2024	Nov 17, 2024	Jun 12, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001349338.3:c.1547del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001336267.1:p.Asn516fs	frameshift
NM_001244808.3:c.1544del	NP_001231737.1:p.Asn515fs	frameshift
NM_001244810.2:c.1531-480del		intron variant
NM_001244812.3:c.1319del	NP_001231741.1:p.Asn440fs	frameshift
NM_001244813.3:c.1247del	NP_001231742.1:p.Asn416fs	frameshift
NM_001244814.3:c.1547del	NP_001231743.1:p.Asn516fs	frameshift
NM_001244815.2:c.1247del	NP_001231744.2:p.Asn416fs	frameshift
NM_001244816.2:c.1547del	NP_001231745.1:p.Asn516fs	frameshift
NM_001349337.2:c.1244del	NP_001336266.2:p.Asn415fs	frameshift
NM_001349340.3:c.1547del	NP_001336269.1:p.Asn516fs	frameshift
NM_001349341.3:c.1544del	NP_001336270.1:p.Asn515fs	frameshift
NM_001349342.3:c.1247del	NP_001336271.1:p.Asn416fs	frameshift
NM_001349343.3:c.1244del	NP_001336272.1:p.Asn415fs	frameshift
NM_001349344.3:c.1244del	NP_001336273.1:p.Asn415fs	frameshift
NM_001370548.1:c.1244del	NP_001357477.1:p.Asn415fs	frameshift
NM_032682.6:c.1547del	NP_116071.2:p.Asn516fs	frameshift
NR_146142.3:n.2063del		non-coding transcript variant
NR_146143.3:n.2060del		non-coding transcript variant
NC_000003.12:g.70972661del
NC_000003.11:g.71021812del
NG_028243.1:g.616330del

... more HGVS ... less HGVS

Protein change

N415fs, N416fs, N440fs, N515fs, N516fs

Other names

Canonical SPDI

NC_000003.12:70972659:TT:T

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	840	919

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.
Intellectual disability-severe speech delay-mild dysmorphism syndrome	Likely pathogenic (1)	criteria provided, single submitter	Jun 12, 2023	RCV004785051.1

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.
Likely Pathogenic (Jun 12, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Intellectual disability-severe speech delay-mild dysmorphism syndrome (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center Accession: SCV005397511.1 First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024	Comment: This sequence variant is a single nucleotide deletion (delT) in exon 18 of 21 of the FOXP1 gene and results in an early termition codon … (more) This sequence variant is a single nucleotide deletion (delT) in exon 18 of 21 of the FOXP1 gene and results in an early termition codon 11 amino acids downstream of the frameshift at Asn516. This variant is predicted to generate a non-functiol allele through either the expression of a truncated protein or a loss of FOXP1 expression due to nonsense mediated decay. This is a novel variant that is absent from ClinVar and has not been observed in the literature in individuals with FOXP1-related disorders, to our knowledge. This variant is absent from the gnomAD population database (0/~250,000 alleles). Haploinsufficiency in FOXP1 is a known mechanism of disease. Based upon the evidence, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PVS1 (less)

Comment:

This sequence variant is a single nucleotide deletion (delT) in exon 18 of 21 of the FOXP1 gene and results in an early termition codon 11 amino acids downstream of the frameshift at Asn516. This variant is predicted to generate a non-functiol allele through either the expression of a truncated protein or a loss of FOXP1 expression due to nonsense mediated decay. This is a novel variant that is absent from ClinVar and has not been observed in the literature in individuals with FOXP1-related disorders, to our knowledge. This variant is absent from the gnomAD population database (0/~250,000 alleles). Haploinsufficiency in FOXP1 is a known mechanism of disease. Based upon the evidence, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PVS1

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Nov 19, 2024

ClinVar Genomic variation as it relates to human health

NM_001349338.3(FOXP1):c.1547del (p.Asn516fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...