rs139938997
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_144687.4(NLRP12):c.2185G>T(p.Gly729Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_144687.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NLRP12 | ENST00000324134.11 | c.2185G>T | p.Gly729Trp | missense_variant | Exon 4 of 10 | 1 | NM_144687.4 | ENSP00000319377.6 | ||
NLRP12 | ENST00000345770.9 | c.2188G>T | p.Gly730Trp | missense_variant | Exon 4 of 9 | 1 | ENSP00000341428.5 | |||
NLRP12 | ENST00000391772.1 | c.2188G>T | p.Gly730Trp | missense_variant | Exon 4 of 7 | 1 | ENSP00000375652.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251234Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135828
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29AN XY: 727232
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 2 Uncertain:1
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. 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 NLRP12 protein function. ClinVar contains an entry for this variant (Variation ID: 579529). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. This variant is present in population databases (rs139938997, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 729 of the NLRP12 protein (p.Gly729Trp). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at