rs122467173
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4
The NM_014009.4(FOXP3):c.970T>G(p.Phe324Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,093,706 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F324L) has been classified as Likely pathogenic.
Frequency
Consequence
NM_014009.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXP3 | NM_014009.4 | c.970T>G | p.Phe324Val | missense_variant, splice_region_variant | 10/12 | ENST00000376207.10 | |
FOXP3 | NM_001114377.2 | c.865T>G | p.Phe289Val | missense_variant, splice_region_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXP3 | ENST00000376207.10 | c.970T>G | p.Phe324Val | missense_variant, splice_region_variant | 10/12 | 1 | NM_014009.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome AF: 0.00000183 AC: 2AN: 1093706Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 359316
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | FOXP3: PM2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Feb 04, 2022 | - - |
Insulin-dependent diabetes mellitus secretory diarrhea syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2023 | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 324 of the FOXP3 protein (p.Phe324Val). This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1677891). This variant has not been reported in the literature in individuals affected with FOXP3-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at