19-55898914-C-G

Variant names:

• chr19-55898914-C-G
• rs1206481676
• NM_176810.2:c.2813G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_176810.2(NLRP13):​c.2813G>C​(p.Arg938Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NLRP13 NM_176810.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.69
• Publications: 0 publications found

Genes affected

NLRP13 (HGNC:22937): (NLR family pyrin domain containing 13) This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07122499).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176810.2. 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
	NLRP13	NM_176810.2	MANE Select	c.2813G>C	p.Arg938Thr	missense	Exon 10 of 11	NP_789780.2	Q86W25
	NLRP13	NM_001321057.1		c.2813G>C	p.Arg938Thr	missense	Exon 10 of 12	NP_001307986.1	Q86W25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP13	ENST00000342929.4	TSL:1 MANE Select	c.2813G>C	p.Arg938Thr	missense	Exon 10 of 11	ENSP00000343891.3	Q86W25
	NLRP13	ENST00000850974.1		c.2975G>C	p.Arg992Thr	missense	Exon 11 of 13	ENSP00000521056.1
	NLRP13	ENST00000588751.5	TSL:5	c.2813G>C	p.Arg938Thr	missense	Exon 10 of 12	ENSP00000467899.1	A0A0C4DGQ4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453260 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722828

African (AFR) AF: 0.00 AC: 0 AN: 32964

American (AMR) AF: 0.00 AC: 0 AN: 41640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25850

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 84324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109790

Other (OTH) AF: 0.00 AC: 0 AN: 60028

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.068
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.4
DANN	Benign	0.14
DEOGEN2	Benign	0.00049	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00087	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.76	N
PhyloP100		-1.7
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.11
Sift	Benign	0.56	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.47		Loss of phosphorylation at T937 (P = 0.1507)
MVP		0.22
MPC		0.018
ClinPred		0.053	T
GERP RS		-5.4
Varity_R		0.036
gMVP		0.30
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1206481676; hg19: chr19-56410280;