rs201136106
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2
The NM_144687.4(NLRP12):c.2171C>T(p.Ala724Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A724A) has been classified as Likely benign.
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP12 | NM_144687.4 | c.2171C>T | p.Ala724Val | missense_variant | 4/10 | ENST00000324134.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP12 | ENST00000324134.11 | c.2171C>T | p.Ala724Val | missense_variant | 4/10 | 1 | NM_144687.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251376Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135878
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727242
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 569082). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. This variant is present in population databases (rs201136106, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 724 of the NLRP12 protein (p.Ala724Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at