Variant 19-55898825-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_176810.2(NLRP13):c.2902G>A(p.Gly968Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NLRP13
NM_176810.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Variant links:

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]

NLRP13 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP13	NM_176810.2 linkuse as main transcript	c.2902G>A	p.Gly968Arg	missense_variant	10/11	ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1 linkuse as main transcript	c.2902G>A	p.Gly968Arg	missense_variant	10/12		NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4 linkuse as main transcript	c.2902G>A	p.Gly968Arg	missense_variant	10/11	1	NM_176810.2	ENSP00000343891.3		Q86W25
NLRP13	ENST00000588751.5 linkuse as main transcript	c.2902G>A	p.Gly968Arg	missense_variant	10/12	5		ENSP00000467899.1		A0A0C4DGQ4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.2902G>A (p.G968R) alteration is located in exon 10 (coding exon 10) of the NLRP13 gene. This alteration results from a G to A substitution at nucleotide position 2902, causing the glycine (G) at amino acid position 968 to be replaced by an arginine (R). 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

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

0.014

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.057

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.0083

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.3

.;M

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-7.8

.;D

REVEL

Benign

0.26

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.95

.;P

Vest4

0.66

MutPred

0.87

Loss of ubiquitination at K970 (P = 0.1041);Loss of ubiquitination at K970 (P = 0.1041);

MVP

0.69

MPC

0.11

ClinPred

0.94

GERP RS

1.8

Varity_R

0.54

gMVP

0.61

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over