chrX-49251359-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_014009.4(FOXP3):c.1271G>A(p.Cys424Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. C424?) has been classified as Likely pathogenic.
Frequency
Consequence
NM_014009.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXP3 | NM_014009.4 | c.1271G>A | p.Cys424Tyr | missense_variant | 12/12 | ENST00000376207.10 | |
FOXP3 | NM_001114377.2 | c.1166G>A | p.Cys389Tyr | missense_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXP3 | ENST00000376207.10 | c.1271G>A | p.Cys424Tyr | missense_variant | 12/12 | 1 | NM_014009.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
Insulin-dependent diabetes mellitus secretory diarrhea syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego | - | This variant has been previously reported as a hemizygous change in patients with Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked (IPEX) Syndrome (PMID: 16990602, 30443250). In vitro studies demonstrate that this variant impairs the transcriptional repressor activity of FOXP3 (PMID: 1692095). It is absent from the gnomAD population database and thus is presumed to be rare. In silico tools used to predict the effect of this variant on protein function yield discordant results. Analysis of the maternal sample was negative for the variant, indicating the variant likely occurred as a de novo event. Based on the available evidence, the c.1271G>A (p.Cys424Tyr) variant is classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.