rs536840312
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001243133.2(NLRP3):c.2095C>T(p.Leu699Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,290 control chromosomes in the GnomAD database, with no homozygous occurrence. 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_001243133.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP3 | NM_001243133.2 | c.2095C>T | p.Leu699Phe | missense_variant | 4/10 | ENST00000336119.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP3 | ENST00000336119.8 | c.2095C>T | p.Leu699Phe | missense_variant | 4/10 | 1 | NM_001243133.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250444Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135498
GnomAD4 exome Cov.: 37
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74462
ClinVar
Submissions by phenotype
Cryopyrin associated periodic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 578380). This variant has not been reported in the literature in individuals affected with NLRP3-related conditions. This variant is present in population databases (rs536840312, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 701 of the NLRP3 protein (p.Leu701Phe). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at