chrX-49251389-C-T
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2
The NM_014009.4(FOXP3):c.1241G>A(p.Arg414His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,209,860 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.00013 ( 0 hom. 41 hem. )
Consequence
FOXP3
NM_014009.4 missense
NM_014009.4 missense
Scores
2
4
11
Clinical Significance
Conservation
PhyloP100: 2.49
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 Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.27564973).
BP6
Variant X-49251389-C-T is Benign according to our data. Variant chrX-49251389-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 763524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAdExome4 at 41 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOXP3 | NM_014009.4 | c.1241G>A | p.Arg414His | missense_variant | 12/12 | ENST00000376207.10 | NP_054728.2 | |
FOXP3 | NM_001114377.2 | c.1136G>A | p.Arg379His | missense_variant | 11/11 | NP_001107849.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FOXP3 | ENST00000376207.10 | c.1241G>A | p.Arg414His | missense_variant | 12/12 | 1 | NM_014009.4 | ENSP00000365380 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000534 AC: 6AN: 112316Hom.: 0 Cov.: 22 AF XY: 0.0000290 AC XY: 1AN XY: 34476
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GnomAD3 exomes AF: 0.0000664 AC: 12AN: 180641Hom.: 0 AF XY: 0.0000916 AC XY: 6AN XY: 65497
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GnomAD4 exome AF: 0.000129 AC: 142AN: 1097544Hom.: 0 Cov.: 31 AF XY: 0.000113 AC XY: 41AN XY: 362950
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GnomAD4 genome AF: 0.0000534 AC: 6AN: 112316Hom.: 0 Cov.: 22 AF XY: 0.0000290 AC XY: 1AN XY: 34476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Insulin-dependent diabetes mellitus secretory diarrhea syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 22, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 30, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;T;.;.;.
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;.;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
D;D;D;P;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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