rs2066029351

Variant names:

• chrX-49251336-AGGGGC-A
• NM_014009.4:c.1289_1293delGCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_014009.4(FOXP3):​c.1289_1293delGCCCC​(p.Gly430ValfsTer27) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: FOXP3 NM_014009.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63
• 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: ClinGen, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0054 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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.1289_1293delGCCCC	p.Gly430ValfsTer27	frameshift	Exon 12 of 12	NP_054728.2
	FOXP3	NM_001114377.2		c.1184_1188delGCCCC	p.Gly395ValfsTer27	frameshift	Exon 11 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.1289_1293delGCCCC	p.Gly430ValfsTer27	frameshift	Exon 12 of 12	ENSP00000365380.4	Q9BZS1-1
	FOXP3	ENST00000518685.6	TSL:1	c.1208_1212delGCCCC	p.Gly403ValfsTer1	frameshift	Exon 10 of 10	ENSP00000428952.2	Q9BZS1-4
	FOXP3	ENST00000557224.6	TSL:2	c.1364_1368delGCCCC	p.Gly455ValfsTer1	frameshift	Exon 10 of 10	ENSP00000451208.1	Q9BZS1-3

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6

Splicing

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

Other links and lift over

hg19: chrX-49107797;