FOXP3 p.Gly53Arg

Variant names:

• chrX-49258349-C-G
• NM_014009.4:c.157G>C
• FOXP3 p.Gly53Arg

Your query was ambiguous. Multiple possible variants found:

• chrX-49258349-C-G
• chrX-49258349-C-T
• chrX-49258347-CCC-ACG
• chrX-49258347-CCC-GCG
• chrX-49258347-CCC-TCG
• chrX-49258347-CCC-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014009.4(FOXP3):​c.157G>C​(p.Gly53Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: FOXP3 NM_014009.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000290184 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26264232).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014009.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP3	NM_014009.4	MANE Select	c.157G>C	p.Gly53Arg	missense	Exon 2 of 12	NP_054728.2
	FOXP3	NM_001114377.2		c.157G>C	p.Gly53Arg	missense	Exon 2 of 11	NP_001107849.1	Q9BZS1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP3	ENST00000376207.10	TSL:1 MANE Select	c.157G>C	p.Gly53Arg	missense	Exon 2 of 12	ENSP00000365380.4	Q9BZS1-1
	FOXP3	ENST00000518685.6	TSL:1	c.157G>C	p.Gly53Arg	missense	Exon 1 of 10	ENSP00000428952.2	Q9BZS1-4
	ENSG00000290184	ENST00000703450.1		c.157G>C	p.Gly53Arg	missense	Exon 4 of 4	ENSP00000515301.1	A0A494C1K1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.61	D
MutationAssessor	Benign	0.90	L
PhyloP100		2.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.80	N
REVEL	Uncertain	0.38
Sift	Benign	0.035	D
Sift4G	Benign	0.55	T
PromoterAI		0.028	Neutral
Varity_R		0.10
gMVP		0.16
Mutation Taster		=88/12	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-49114806;