X-49259429-T-C

Variant names:

• chrX-49259429-T-C
• rs2232365
• NM_014009.4:c.-22-902A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014009.4(FOXP3):​c.-22-902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (15614 hom., 18214 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: FOXP3 NM_014009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.68
• Publications: 110 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: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P

ENSG00000290184 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP3	NM_014009.4	c.-22-902A>G		intron_variant	Intron 1 of 11	ENST00000376207.10	NP_054728.2
FOXP3	NM_001114377.2	c.-22-902A>G		intron_variant	Intron 1 of 10		NP_001107849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP3	ENST00000376207.10	c.-22-902A>G		intron_variant	Intron 1 of 11	1	NM_014009.4	ENSP00000365380.4
ENSG00000290184	ENST00000703450.1	c.-22-902A>G		intron_variant	Intron 3 of 3			ENSP00000515301.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 66596 AN: 108210 Hom.: 15616 Cov.: 21

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.582

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.616 AC: 66656 AN: 108266 Hom.: 15614 Cov.: 21 AF XY: 0.593 AC XY: 18214 AN XY: 30696

African (AFR) AF: 0.781 AC: 23106 AN: 29601

American (AMR) AF: 0.477 AC: 4873 AN: 10213

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 1522 AN: 2609

East Asian (EAS) AF: 0.381 AC: 1299 AN: 3408

South Asian (SAS) AF: 0.575 AC: 1401 AN: 2435

European-Finnish (FIN) AF: 0.486 AC: 2687 AN: 5526

Middle Eastern (MID) AF: 0.608 AC: 129 AN: 212

European-Non Finnish (NFE) AF: 0.584 AC: 30416 AN: 52116

Other (OTH) AF: 0.585 AC: 874 AN: 1493

Alfa AF: 0.613 Hom.: 11563

Bravo AF: 0.618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0040
DANN	Benign	0.28
PhyloP100		-5.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2232365; hg19: chrX-49115886;