chr11-7959964-C-T

Variant names:

• chr11-7959964-C-T
• rs868150302
• NM_001391958.1:c.1648G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.345
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391958.1. 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
	NLRP10	NM_001391958.1	MANE Select	c.1648G>A	p.Glu550Lys	missense	Exon 3 of 3	NP_001378887.1	Q86W26
	NLRP10	NM_176821.4		c.1648G>A	p.Glu550Lys	missense	Exon 2 of 2	NP_789791.1	Q86W26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP10	ENST00000691676.1	MANE Select	c.1648G>A	p.Glu550Lys	missense	Exon 3 of 3	ENSP00000509542.1	Q86W26
	NLRP10	ENST00000328600.3	TSL:1	c.1648G>A	p.Glu550Lys	missense	Exon 2 of 2	ENSP00000327763.2	Q86W26

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.34
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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

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