NM_144687.4:c.3185G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_144687.4(NLRP12):c.3185G>A(p.Ter1062Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
NLRP12
NM_144687.4 stop_retained
NM_144687.4 stop_retained
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.39
Publications
0 publications found
Genes affected
NLRP12 (HGNC:22938): (NLR family pyrin domain containing 12) This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]
NLRP12 Gene-Disease associations (from GenCC):
- familial cold autoinflammatory syndrome 2Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 19-53794050-C-T is Benign according to our data. Variant chr19-53794050-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2753559.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.39 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_144687.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NLRP12 | NM_144687.4 | MANE Select | c.3185G>A | p.Ter1062Ter | stop_retained | Exon 10 of 10 | NP_653288.1 | P59046-1 | |
| NLRP12 | NM_001277126.2 | c.3188G>A | p.Ter1063Ter | stop_retained | Exon 10 of 10 | NP_001264055.1 | P59046-7 | ||
| NLRP12 | NM_001277129.1 | c.3014G>A | p.Ter1005Ter | stop_retained | Exon 9 of 9 | NP_001264058.1 | P59046-6 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NLRP12 | ENST00000324134.11 | TSL:1 MANE Select | c.3185G>A | p.Ter1062Ter | stop_retained | Exon 10 of 10 | ENSP00000319377.6 | P59046-1 | |
| NLRP12 | ENST00000391773.8 | TSL:1 | c.3188G>A | p.Ter1063Ter | stop_retained | Exon 10 of 10 | ENSP00000375653.1 | P59046-7 | |
| NLRP12 | ENST00000345770.9 | TSL:1 | c.3020G>A | p.Ter1007Ter | stop_retained | Exon 9 of 9 | ENSP00000341428.5 | A0A0C4DH17 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00000795 AC: 2AN: 251484 AF XY: 0.0000147 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
251484
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459138Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726112 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1459138
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726112
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33422
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26112
East Asian (EAS)
AF:
AC:
0
AN:
39694
South Asian (SAS)
AF:
AC:
0
AN:
86222
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1109484
Other (OTH)
AF:
AC:
0
AN:
60300
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Familial cold autoinflammatory syndrome 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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