NM_144687.4:c.910C>T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_144687.4(NLRP12):c.910C>T(p.His304Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,614,044 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_144687.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NLRP12 | ENST00000324134.11 | c.910C>T | p.His304Tyr | missense_variant | Exon 3 of 10 | 1 | NM_144687.4 | ENSP00000319377.6 | ||
NLRP12 | ENST00000345770.9 | c.910C>T | p.His304Tyr | missense_variant | Exon 3 of 9 | 1 | ENSP00000341428.5 | |||
NLRP12 | ENST00000391772.1 | c.910C>T | p.His304Tyr | missense_variant | Exon 3 of 7 | 1 | ENSP00000375652.1 |
Frequencies
GnomAD3 genomes AF: 0.00377 AC: 574AN: 152072Hom.: 4 Cov.: 31
GnomAD3 exomes AF: 0.00432 AC: 1086AN: 251246Hom.: 4 AF XY: 0.00430 AC XY: 584AN XY: 135840
GnomAD4 exome AF: 0.00384 AC: 5619AN: 1461852Hom.: 21 Cov.: 40 AF XY: 0.00372 AC XY: 2702AN XY: 727226
GnomAD4 genome AF: 0.00377 AC: 574AN: 152192Hom.: 4 Cov.: 31 AF XY: 0.00453 AC XY: 337AN XY: 74412
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 2 Uncertain:1Benign:5
- -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
- -
- -
This variant has been reported in the literature in several individuals with features of immunodeficiency or autoimmunity, including periodic fevers, in the heterozygous and compound heterozygous state (Borte 2014 PMID: 25064829, Rusmini 2016 PMID: 26386126, Cetinkaya 2018 PMID: 29307770, Kostik 2018 PMID: 29500522, Ledesma 2019 PMID: 31836009, Suspitsin 2020 PMID: 32441320). This variant is present in the Genome Aggregation Database (Highest reported MAF: 2.1% [515/25100], including 3 homozygotes; https://gnomad.broadinstitute.org/variant/19-54314003-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign (Variation ID: 262532). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant suggests that this variant does not cause Mendelian disease but requires further evidence. Therefore, this variant is classified as likely benign. -
- -
not provided Benign:3
NLRP12: BP4, BS1, BS2 -
- -
- -
not specified Benign:1
- -
Autoinflammatory syndrome Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at