rs202104062

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153447.4(NLRP5):​c.71C>G​(p.Thr24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,596,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T24I) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000032 ( 0 hom. )

Consequence

NLRP5
NM_153447.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.446
Variant links:
Genes affected
NLRP5 (HGNC:21269): (NLR family pyrin domain containing 5) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). Expression of this gene is restricted to the oocyte. A mouse gene that encodes a maternal oocyte protein, similar to this encoded protein, is required for normal early embryogenesis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NLRP5NM_153447.4 linkc.71C>G p.Thr24Ser missense_variant Exon 2 of 15 ENST00000390649.8 NP_703148.4 P59047

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NLRP5ENST00000390649.8 linkc.71C>G p.Thr24Ser missense_variant Exon 2 of 15 1 NM_153447.4 ENSP00000375063.3 P59047
NLRP5ENST00000597673.1 linkn.-11C>G upstream_gene_variant 5 ENSP00000471494.1 M0R0W4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000424
AC:
1
AN:
235690
Hom.:
0
AF XY:
0.00000783
AC XY:
1
AN XY:
127790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000920
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000319
AC:
46
AN:
1444152
Hom.:
0
Cov.:
31
AF XY:
0.0000362
AC XY:
26
AN XY:
717288
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000407
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000828
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
6.1
DANN
Benign
0.34
DEOGEN2
Benign
0.027
.;T
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.33
T;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
.;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.38
.;N
REVEL
Benign
0.073
Sift
Pathogenic
0.0
.;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.81
.;P
Vest4
0.16
MutPred
0.27
Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP
0.51
MPC
0.021
ClinPred
0.083
T
GERP RS
0.27
Varity_R
0.055
gMVP
0.050

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.34
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.34
Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs202104062; hg19: chr19-56515090; API