chr19-55904951-T-A

Position:

• chr19-55904951-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_176810.2(NLRP13):​c.2609A>T​(p.Glu870Val) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NLRP13 NM_176810.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26057154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP13	NM_176810.2	c.2609A>T	p.Glu870Val	missense_variant	8/11	ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1	c.2609A>T	p.Glu870Val	missense_variant	8/12		NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4	c.2609A>T	p.Glu870Val	missense_variant	8/11	1	NM_176810.2	ENSP00000343891.3
NLRP13	ENST00000588751.5	c.2609A>T	p.Glu870Val	missense_variant	8/12	5		ENSP00000467899.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 05, 2024

The c.2609A>T (p.E870V) alteration is located in exon 8 (coding exon 8) of the NLRP13 gene. This alteration results from a A to T substitution at nucleotide position 2609, causing the glutamic acid (E) at amino acid position 870 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.4	.;D
REVEL	Benign	0.13
Sift	Uncertain	0.0060	.;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.75	.;P
Vest4		0.34
MutPred		0.50		Loss of methylation at K866 (P = 0.1237);Loss of methylation at K866 (P = 0.1237);
MVP		0.57
MPC		0.099
ClinPred		0.97	D
GERP RS		2.3
Varity_R		0.29
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-56416317;