chr10-89010783-T-G
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4
The NM_000043.6(FAS):c.536T>G(p.Leu179Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000043.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Splenomegaly Pathogenic:1
- -
not provided Pathogenic:1
FAS: PM2, PP4:Moderate, PS4:Moderate -
Autoimmune lymphoproliferative syndrome type 1 Pathogenic:1
This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 179 of the FAS protein (p.Leu179Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autoimmune lymphoproliferative syndrome (ALPS) (internal data). ClinVar contains an entry for this variant (Variation ID: 523313). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FAS protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at