19-55902290-G-A

Position:

• chr19-55902290-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_176810.2(NLRP13):​c.2619-85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000573 in 1,082,038 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000054 (1 hom.)
• Consequence: NLRP13 NM_176810.2 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.744

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP13	NM_176810.2	c.2619-85C>T		intron_variant		ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1	c.2619-85C>T		intron_variant			NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4	c.2619-85C>T		intron_variant		1	NM_176810.2	ENSP00000343891.3
NLRP13	ENST00000588751.5	c.2619-85C>T		intron_variant		5		ENSP00000467899.1

Frequencies

GnomAD3 genomes AF: 0.0000775 AC: 8 AN: 103240 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000866

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000542 AC: 53 AN: 978668 Hom.: 1 AF XY: 0.0000387 AC XY: 19 AN XY: 490394

Gnomad4 AFR exome AF: 0.000349

Gnomad4 AMR exome AF: 0.000299

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000122

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000406

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000871 AC: 9 AN: 103370 Hom.: 0 Cov.: 27 AF XY: 0.000136 AC XY: 7 AN XY: 51320

Gnomad4 AFR AF: 0.0000738

Gnomad4 AMR AF: 0.000192

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000282

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000866

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000642

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Human Evolutionary Genetics, Institut Pasteur

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.94
DANN	Benign	0.42

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: rs199476256; hg19: chr19-56413656;