X-49251322-TTGATCTTGAGGTCAGGGG-CA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_014009.4(FOXP3):​c.1290_*12delinsTG variant causes a stop lost, 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 22)

Consequence

FOXP3
NM_014009.4 stop_lost, 3_prime_UTR

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.96
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Stoplost variant. No alternative stopcodon identified downstream, so we assume a Nonstop Mediated Decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-49251322-TTGATCTTGAGGTCAGGGG-CA is Pathogenic according to our data. Variant chrX-49251322-TTGATCTTGAGGTCAGGGG-CA is described in ClinVar as [Pathogenic]. Clinvar id is 11408.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FOXP3NM_014009.4 linkuse as main transcriptc.1290_*12delinsTG stop_lost, 3_prime_UTR_variant 12/12 ENST00000376207.10 NP_054728.2
FOXP3NM_001114377.2 linkuse as main transcriptc.1185_*12delinsTG stop_lost, 3_prime_UTR_variant 11/11 NP_001107849.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FOXP3ENST00000376207.10 linkuse as main transcriptc.1290_*12delinsTG stop_lost, 3_prime_UTR_variant 12/121 NM_014009.4 ENSP00000365380 P1Q9BZS1-1

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

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Insulin-dependent diabetes mellitus secretory diarrhea syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 01, 2001- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-49107783; API