rs143882052
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_032977.4(CASP10):c.683C>T(p.Pro228Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000578 in 1,606,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P228S) has been classified as Uncertain significance.
Frequency
Consequence
NM_032977.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASP10 | NM_032977.4 | c.683C>T | p.Pro228Leu | missense_variant, splice_region_variant | 5/10 | ENST00000286186.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASP10 | ENST00000286186.11 | c.683C>T | p.Pro228Leu | missense_variant, splice_region_variant | 5/10 | 1 | NM_032977.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000223 AC: 56AN: 251240Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135812
GnomAD4 exome AF: 0.000613 AC: 892AN: 1454454Hom.: 0 Cov.: 28 AF XY: 0.000581 AC XY: 421AN XY: 724084
GnomAD4 genome ? AF: 0.000237 AC: 36AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74392
ClinVar
Submissions by phenotype
Autoimmune lymphoproliferative syndrome type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 228 of the CASP10 protein (p.Pro228Leu). This variant is present in population databases (rs143882052, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of autoimmune lymphoproliferative syndrome (PMID: 34329798). ClinVar contains an entry for this variant (Variation ID: 535761). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at