chr11-70203505-TCGAGCAG-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_003824.4(FADD):c.52_58delAGCGAGC(p.Ser18fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,606,574 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
FADD
NM_003824.4 frameshift
NM_003824.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.254
Genes affected
FADD (HGNC:3573): (Fas associated via death domain) The protein encoded by this gene is an adaptor molecule that interacts with various cell surface receptors and mediates cell apoptotic signals. Through its C-terminal death domain, this protein can be recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and thus it participates in the death signaling initiated by these receptors. Interaction of this protein with the receptors unmasks the N-terminal effector domain of this protein, which allows it to recruit caspase-8, and thereby activate the cysteine protease cascade. Knockout studies in mice also suggest the importance of this protein in early T cell development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-70203505-TCGAGCAG-T is Pathogenic according to our data. Variant chr11-70203505-TCGAGCAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 242497.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| FADD | NM_003824.4 | c.52_58delAGCGAGC | p.Ser18fs | frameshift_variant | 1/2 | ENST00000301838.5 | NP_003815.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| FADD | ENST00000301838.5 | c.52_58delAGCGAGC | p.Ser18fs | frameshift_variant | 1/2 | 1 | NM_003824.4 | ENSP00000301838.5 |
Frequencies
GnomAD3 genomes 0.0000132 AC: 2AN: 152032Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1454542Hom.: 0 AF XY: 0.00000277 AC XY: 2AN XY: 723220
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GnomAD4 genome 0.0000132 AC: 2AN: 152032Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74262
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
FADD-related immunodeficiency Pathogenic:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 30, 2021 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at