rs752809784
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2
The NM_144687.4(NLRP12):c.815G>A(p.Trp272Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_144687.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP12 | NM_144687.4 | c.815G>A | p.Trp272Ter | stop_gained | 3/10 | ENST00000324134.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP12 | ENST00000324134.11 | c.815G>A | p.Trp272Ter | stop_gained | 3/10 | 1 | NM_144687.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251194Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135798
GnomAD4 exome AF: 0.000127 AC: 186AN: 1461826Hom.: 1 Cov.: 40 AF XY: 0.000122 AC XY: 89AN XY: 727226
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2023 | This sequence change creates a premature translational stop signal (p.Trp272*) in the NLRP12 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NLRP12 cause disease. This variant is present in population databases (rs752809784, gnomAD 0.004%). 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. ClinVar contains an entry for this variant (Variation ID: 572583). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at