rs796052177

Positions:

• chr19-55932122-C-A
• chr19-55932122-C-T

Variant summary

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

The NM_176810.2(NLRP13):​c.190G>T​(p.Asp64Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NLRP13 NM_176810.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP13	NM_176810.2	c.190G>T	p.Asp64Tyr	missense_variant	1/11	ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1	c.190G>T	p.Asp64Tyr	missense_variant	1/12		NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4	c.190G>T	p.Asp64Tyr	missense_variant	1/11	1	NM_176810.2	ENSP00000343891.3
NLRP13	ENST00000588751.5	c.190G>T	p.Asp64Tyr	missense_variant	1/12	5		ENSP00000467899.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.0	.;D
REVEL	Benign	0.18
Sift	Benign	0.057	.;T
Sift4G	Benign	0.075	T;D
Polyphen		1.0	.;D
Vest4		0.39
MutPred		0.60		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP		0.58
MPC		0.14
ClinPred		0.96	D
GERP RS		-0.26
Varity_R		0.13
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs796052177; hg19: chr19-56443488;