rs760120881
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_144687.4(NLRP12):c.2750C>T(p.Thr917Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NLRP12 | NM_144687.4 | c.2750C>T | p.Thr917Ile | missense_variant | 7/10 | ENST00000324134.11 | NP_653288.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NLRP12 | ENST00000324134.11 | c.2750C>T | p.Thr917Ile | missense_variant | 7/10 | 1 | NM_144687.4 | ENSP00000319377 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151942Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250626Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135544
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461846Hom.: 0 Cov.: 35 AF XY: 0.0000289 AC XY: 21AN XY: 727224
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151942Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74192
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 20, 2023 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 424097). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. This variant is present in population databases (rs760120881, gnomAD 0.002%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 917 of the NLRP12 protein (p.Thr917Ile). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2017 | The T917I variant in the NLRP12 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T917I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T917I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T917I as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at