Variant X-49251390-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP6_ModerateBS2

The NM_014009.4(FOXP3):c.1240C>T(p.Arg414Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000678 in 1,209,894 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R414H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000070 ( 0 hom. 33 hem. )

Consequence

FOXP3
NM_014009.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.59

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]

FOXP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM1

In a DNA_binding_region Fork-head (size 86) in uniprot entity FOXP3_HUMAN there are 22 pathogenic changes around while only 3 benign (88%) in NM_014009.4

BP6

Variant X-49251390-G-A is Benign according to our data. Variant chrX-49251390-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1151373.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXP3	NM_014009.4 linkuse as main transcript	c.1240C>T	p.Arg414Cys	missense_variant	12/12	ENST00000376207.10
FOXP3	NM_001114377.2 linkuse as main transcript	c.1135C>T	p.Arg379Cys	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXP3	ENST00000376207.10 linkuse as main transcript	c.1240C>T	p.Arg414Cys	missense_variant	12/12	1	NM_014009.4	P1	Q9BZS1-1

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112204

Hom.:

Cov.:

AF XY:

0.0000873

AC XY:

AN XY:

34380

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000221

AC:

AN:

180919

Hom.:

AF XY:

0.0000456

AC XY:

AN XY:

65737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000701

AC:

AN:

1097690

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

363092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000903

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112204

Hom.:

Cov.:

AF XY:

0.0000873

AC XY:

AN XY:

34380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000941

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Insulin-dependent diabetes mellitus secretory diarrhea syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.050

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Pathogenic

0.85

D;.;T;.;.;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D;D;.;D

M_CAP

Pathogenic

0.94

MetaRNN

Uncertain

0.59

D;D;D;D;D;D

MetaSVM

Pathogenic

0.95

MutationAssessor

Uncertain

2.1

M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.3

D;D;.;D;D;D

REVEL

Pathogenic

0.84

Sift

Benign

0.041

D;D;.;D;D;D

Sift4G

Pathogenic

0.0010

D;D;T;T;D;T

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.29

MutPred

0.55

Loss of MoRF binding (P = 0.0064);.;.;.;.;.;

MVP

0.95

MPC

1.4

ClinPred

0.77

GERP RS

4.6

Varity_R

0.56

gMVP

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over