rs122467171
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PM4_SupportingPP5_Very_Strong
The NM_014009.4(FOXP3):c.751_753del(p.Glu251del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 23)
Consequence
FOXP3
NM_014009.4 inframe_deletion
NM_014009.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.14
Genes affected
FOXP3 (HGNC:6106): (forkhead box P3) The protein encoded by this gene is a member of the forkhead/winged-helix family of transcriptional regulators. Defects in this gene are the cause of immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), also known as X-linked autoimmunity-immunodeficiency syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_014009.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant X-49255491-TCTC-T is Pathogenic according to our data. Variant chrX-49255491-TCTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 11413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXP3 | NM_014009.4 | c.751_753del | p.Glu251del | inframe_deletion | 8/12 | ENST00000376207.10 | |
FOXP3 | NM_001114377.2 | c.646_648del | p.Glu216del | inframe_deletion | 7/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXP3 | ENST00000376207.10 | c.751_753del | p.Glu251del | inframe_deletion | 8/12 | 1 | NM_014009.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Insulin-dependent diabetes mellitus secretory diarrhea syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2022 | ClinVar contains an entry for this variant (Variation ID: 11413). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects FOXP3 function (PMID: 17586580). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This variant has been observed in individuals with clinical features of X-linked recessive immunodysregulation, polyendocrinopathy, and enteropathy (IPEX syndrome) (PMID: 11120765, 20537998, 24916357, 30443250, 32531870). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant, c.751_753del, results in the deletion of 1 amino acid(s) of the FOXP3 protein (p.Glu251del), but otherwise preserves the integrity of the reading frame. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2000 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | FOXP3: PS3, PM2, PS4:Moderate, PM4:Supporting, PP1, PP4 - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at