rs17860403
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_032977.4(CASP10):c.853C>T(p.Leu285Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,912 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_032977.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASP10 | NM_032977.4 | c.853C>T | p.Leu285Phe | missense_variant | 8/10 | ENST00000286186.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASP10 | ENST00000286186.11 | c.853C>T | p.Leu285Phe | missense_variant | 8/10 | 1 | NM_032977.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152126Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251314Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135806
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461786Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727206
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152126Hom.: 1 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74304
ClinVar
Submissions by phenotype
Autoimmune lymphoproliferative syndrome type 2A Pathogenic:1Uncertain:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 09, 1999 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2023 | Experimental studies have shown that this missense change affects CASP10 function (PMID: 10412980, 16446975, 27799292). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CASP10 protein function. ClinVar contains an entry for this variant (Variation ID: 7764). This missense change has been observed in individual(s) with clinical features of autoimmune lymphoproliferative syndrome (PMID: 10412980). This variant is present in population databases (rs17860403, gnomAD 0.03%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 285 of the CASP10 protein (p.Leu285Phe). 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. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at