19-55788942-C-A

Variant names:

• chr19-55788942-C-A
• rs73616926
• NM_001394894.2:c.2720G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394894.2(NLRP11):​c.2720G>T​(p.Arg907Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: NLRP11 NM_001394894.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.56
• Publications: 0 publications found

Genes affected

NLRP11 (HGNC:22945): (NLR family pyrin domain containing 11) This gene is a member of the the NOD-like receptor protein (NLRP) gene family and encodes a protein with an N-terminal pyrin death (PYD) domain and nucleoside triphosphate hydrolase (NACHT) domain and a C-terminal leucine-rich repeats (LRR) region. This gene has been shown to regulate caspases in the proinflammatory signal transduction pathway and, based on studies of other members of the NLRP gene family with similar domain structure, is predicted to form part of the multiprotein inflammasome complex. Alternative splicing produces multiple transcript variants encoding distince isoforms. [provided by RefSeq, May 2017]

NLRP11 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394894.2. 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
	NLRP11	NM_001394894.2	MANE Select	c.2720G>T	p.Arg907Leu	missense	Exon 9 of 10	NP_001381823.1	P59045-1
	NLRP11	NM_145007.5		c.2720G>T	p.Arg907Leu	missense	Exon 11 of 12	NP_659444.2	P59045-1
	NLRP11	NM_001385451.2		c.2558G>T	p.Arg853Leu	missense	Exon 10 of 11	NP_001372380.1	P59045-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	ENST00000589093.6	TSL:1 MANE Select	c.2720G>T	p.Arg907Leu	missense	Exon 9 of 10	ENSP00000466285.1	P59045-1
	NLRP11	ENST00000592953.5	TSL:1	c.2423G>T	p.Arg808Leu	missense	Exon 8 of 9	ENSP00000468196.1	P59045-3
	NLRP11	ENST00000590409.5	TSL:1	n.*534G>T		non_coding_transcript_exon	Exon 11 of 12	ENSP00000466582.1	K7EMN8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461864 Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

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	0.097
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.017
DANN	Benign	0.78
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.54	N
PhyloP100		-1.6
PrimateAI	Benign	0.23	T
Sift4G	Benign	0.16	T
Polyphen		0.080	B
Vest4		0.16
MutPred		0.48		Loss of methylation at R907 (P = 0.0438)
MVP		0.39
ClinPred		0.035	T
GERP RS		-5.5
Varity_R		0.060
gMVP		0.31
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: 35

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

Other links and lift over

dbSNP: rs73616926; hg19: chr19-56300308;