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rs142994383

chrX-49258476-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014009.4(FOXP3):c.30G>A(p.Ser10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,179,524 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 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 0.000089 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.000047 ( 0 hom. 15 hem. )

Consequence

FOXP3
NM_014009.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28
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 -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-49258476-C-T is Benign according to our data. Variant chrX-49258476-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 529770.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.28 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAdExome at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXP3NM_014009.4 linkuse as main transcriptc.30G>A p.Ser10= synonymous_variant 2/12 ENST00000376207.10
FOXP3NM_001114377.2 linkuse as main transcriptc.30G>A p.Ser10= synonymous_variant 2/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXP3ENST00000376207.10 linkuse as main transcriptc.30G>A p.Ser10= synonymous_variant 2/121 NM_014009.4 P1Q9BZS1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000886
AC:
10
AN:
112843
Hom.:
0
Cov.:
24
AF XY:
0.0000286
AC XY:
1
AN XY:
34995
show subpopulations
Gnomad AFR
AF:
0.000225
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:
0.0000563
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000761
AC:
10
AN:
131439
Hom.:
0
AF XY:
0.0000563
AC XY:
2
AN XY:
35525
show subpopulations
Gnomad AFR exome
AF:
0.000326
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000298
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000549
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000469
AC:
50
AN:
1066629
Hom.:
0
Cov.:
31
AF XY:
0.0000439
AC XY:
15
AN XY:
341797
show subpopulations
Gnomad4 AFR exome
AF:
0.000117
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000381
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000448
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000886
AC:
10
AN:
112895
Hom.:
0
Cov.:
24
AF XY:
0.0000285
AC XY:
1
AN XY:
35057
show subpopulations
Gnomad4 AFR
AF:
0.000225
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:
0.0000563
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000680

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 submitterclinical testingInvitaeOct 25, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
3.3
Dann
Benign
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs142994383; hg19: chrX-49114933; API