chrX-49251389-C-T

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

Scores

2
4
11

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.49
Variant links:
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]

Genome browser will be placed here

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
FOXP3NM_014009.4 linkuse as main transcriptc.1241G>A p.Arg414His missense_variant 12/12 ENST00000376207.10 NP_054728.2
FOXP3NM_001114377.2 linkuse as main transcriptc.1136G>A p.Arg379His missense_variant 11/11 NP_001107849.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FOXP3ENST00000376207.10 linkuse as main transcriptc.1241G>A p.Arg414His missense_variant 12/121 NM_014009.4 ENSP00000365380 P1Q9BZS1-1

Frequencies

GnomAD3 genomes
AF:
0.0000534
AC:
6
AN:
112316
Hom.:
0
Cov.:
22
AF XY:
0.0000290
AC XY:
1
AN XY:
34476
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000279
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000940
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000664
AC:
12
AN:
180641
Hom.:
0
AF XY:
0.0000916
AC XY:
6
AN XY:
65497
show subpopulations
Gnomad AFR exome
AF:
0.000155
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000145
Gnomad SAS exome
AF:
0.000107
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000745
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000129
AC:
142
AN:
1097544
Hom.:
0
Cov.:
31
AF XY:
0.000113
AC XY:
41
AN XY:
362950
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000663
Gnomad4 SAS exome
AF:
0.0000556
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000160
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000534
AC:
6
AN:
112316
Hom.:
0
Cov.:
22
AF XY:
0.0000290
AC XY:
1
AN XY:
34476
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000279
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000940
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000982
ExAC
AF:
0.0000577
AC:
7

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 22, 2023- -
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsNov 30, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
23
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.58
D;.;T;.;.;.
FATHMM_MKL
Benign
0.54
D
LIST_S2
Uncertain
0.97
D;D;D;D;.;D
M_CAP
Pathogenic
0.80
D
MetaRNN
Benign
0.28
T;T;T;T;T;T
MetaSVM
Uncertain
0.66
D
MutationAssessor
Benign
1.2
L;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.0
N;N;.;N;N;N
REVEL
Uncertain
0.54
Sift
Benign
0.095
T;T;.;T;T;T
Sift4G
Benign
0.11
T;T;T;T;T;T
Polyphen
1.0
D;D;D;P;D;.
Vest4
0.12
MVP
0.96
MPC
1.3
ClinPred
0.19
T
GERP RS
4.6
Varity_R
0.24
gMVP
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782786757; hg19: chrX-49107850; COSMIC: COSV66051211; COSMIC: COSV66051211; API