11-7959964-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001391958.1(NLRP10):​c.1648G>A​(p.Glu550Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NLRP10
NM_001391958.1 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.345
Variant links:
Genes affected
NLRP10 (HGNC:21464): (NLR family pyrin domain containing 10) 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). The protein encoded by this gene belongs to the NALP protein family despite lacking the LRR region. This protein likely plays a regulatory role in the innate immune system. The protein belongs to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. Other experiments indicate that this gene acts as a multifunctional negative regulator of inflammation and apoptosis. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06715953).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NLRP10NM_001391958.1 linkc.1648G>A p.Glu550Lys missense_variant Exon 3 of 3 ENST00000691676.1 NP_001378887.1
NLRP10NM_176821.4 linkc.1648G>A p.Glu550Lys missense_variant Exon 2 of 2 NP_789791.1 Q86W26

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NLRP10ENST00000691676.1 linkc.1648G>A p.Glu550Lys missense_variant Exon 3 of 3 NM_001391958.1 ENSP00000509542.1 Q86W26
NLRP10ENST00000328600.3 linkc.1648G>A p.Glu550Lys missense_variant Exon 2 of 2 1 ENSP00000327763.2 Q86W26

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1648G>A (p.E550K) alteration is located in exon 2 (coding exon 2) of the NLRP10 gene. This alteration results from a G to A substitution at nucleotide position 1648, causing the glutamic acid (E) at amino acid position 550 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.015
N
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.067
T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.043
Sift
Benign
0.24
T
Sift4G
Benign
0.074
T
Polyphen
0.025
B
Vest4
0.13
MutPred
0.39
Loss of ubiquitination at K546 (P = 0.0283);
MVP
0.78
MPC
0.14
ClinPred
0.12
T
GERP RS
0.98
Varity_R
0.053
gMVP
0.10

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs868150302; hg19: chr11-7981511; COSMIC: COSV60779279; COSMIC: COSV60779279; API