rs777390517
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000639.3(FASLG):βc.144_152delβ(p.Pro51_Pro53del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,611,748 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.00016 ( 0 hom., cov: 32)
Exomes π: 0.000014 ( 0 hom. )
Consequence
FASLG
NM_000639.3 inframe_deletion
NM_000639.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.98
Genes affected
FASLG (HGNC:11936): (Fas ligand) This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd4 at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASLG | NM_000639.3 | c.144_152del | p.Pro51_Pro53del | inframe_deletion | 1/4 | ENST00000367721.3 | |
FASLG | NM_001302746.2 | c.144_152del | p.Pro51_Pro53del | inframe_deletion | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASLG | ENST00000367721.3 | c.144_152del | p.Pro51_Pro53del | inframe_deletion | 1/4 | 1 | NM_000639.3 | P1 | |
FASLG | ENST00000340030.4 | c.144_152del | p.Pro51_Pro53del | inframe_deletion | 1/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 151792Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246216Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133516
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459836Hom.: 0 AF XY: 0.00000689 AC XY: 5AN XY: 726104
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GnomAD4 genome ? AF: 0.000165 AC: 25AN: 151912Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74260
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autoimmune lymphoproliferative syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 05, 2022 | This variant, c.144_152del, results in the deletion of 3 amino acid(s) of the FASLG protein (p.Pro51_Pro53del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs777390517, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FASLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 532231). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at