rs111856931

Variant names:

• chrX-49257557-C-A
• rs111856931
• NM_014009.4:c.324G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-49257557-C-A
• chrX-49257557-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_014009.4(FOXP3):​c.324G>T​(p.Thr108Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000465 in 1,074,327 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T108T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000047 (0 hom. 2 hem.)
• Consequence: FOXP3 NM_014009.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-2.48 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP3	NM_014009.4	c.324G>T	p.Thr108Thr	synonymous_variant	Exon 4 of 12	ENST00000376207.10	NP_054728.2
FOXP3	NM_001114377.2	c.219G>T	p.Thr73Thr	synonymous_variant	Exon 3 of 11		NP_001107849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP3	ENST00000376207.10	c.324G>T	p.Thr108Thr	synonymous_variant	Exon 4 of 12	1	NM_014009.4	ENSP00000365380.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000627 AC: 1 AN: 159455 AF XY: 0.0000201

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000465 AC: 5 AN: 1074327 Hom.: 0 Cov.: 32 AF XY: 0.00000577 AC XY: 2 AN XY: 346553

African (AFR) AF: 0.00 AC: 0 AN: 26055

American (AMR) AF: 0.00 AC: 0 AN: 34036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18204

East Asian (EAS) AF: 0.00 AC: 0 AN: 29762

South Asian (SAS) AF: 0.00 AC: 0 AN: 51199

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4011

European-Non Finnish (NFE) AF: 0.00000605 AC: 5 AN: 826384

Other (OTH) AF: 0.00 AC: 0 AN: 44984

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.1
DANN	Benign	0.73
PhyloP100		-2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs111856931; hg19: chrX-49114014;