rs1057519492
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_033004.4(NLRP1):c.160G>A(p.Ala54Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NLRP1
NM_033004.4 missense
NM_033004.4 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 1.55
Genes affected
NLRP1 (HGNC:14374): (NLR family pyrin domain containing 1) This gene encodes a member of the Ced-4 family of apoptosis proteins. Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The encoded protein contains a distinct N-terminal pyrin-like motif, which is possibly involved in protein-protein interactions. This protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to induce apoptosis in cells. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-5583798-C-T is Pathogenic according to our data. Variant chr17-5583798-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 375413.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP1 | NM_033004.4 | c.160G>A | p.Ala54Thr | missense_variant | 1/17 | ENST00000572272.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLRP1 | ENST00000572272.6 | c.160G>A | p.Ala54Thr | missense_variant | 1/17 | 1 | NM_033004.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1405058Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 693658
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1405058
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
693658
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 30, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;N;.;N;.;.;.;N
REVEL
Benign
Sift
Uncertain
D;.;.;D;.;D;.;.;.;D
Sift4G
Uncertain
D;D;.;D;D;D;D;D;D;D
Polyphen
0.94, 0.99, 0.99
.;.;P;P;D;D;D;D;D;P
Vest4
MutPred
Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);Gain of glycosylation at A54 (P = 0.0871);
MVP
MPC
0.77
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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