rs796052177

Variant names:

• chr19-55932122-C-T
• rs796052177
• NM_176810.2:c.190G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_176810.2(NLRP13):​c.190G>A​(p.Asp64Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,022 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 Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NLRP13 NM_176810.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.677
• Publications: 4 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12454036).
• BP6: Variant 19-55932122-C-T is Benign according to our data. Variant chr19-55932122-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 207900.Status of the report is no_assertion_criteria_provided, 0 stars.

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.190G>A	p.Asp64Asn	missense	Exon 1 of 11	NP_789780.2	Q86W25
	NLRP13	NM_001321057.1		c.190G>A	p.Asp64Asn	missense	Exon 1 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.190G>A	p.Asp64Asn	missense	Exon 1 of 11	ENSP00000343891.3	Q86W25
	NLRP13	ENST00000850974.1		c.190G>A	p.Asp64Asn	missense	Exon 1 of 13	ENSP00000521056.1
	NLRP13	ENST00000588751.5	TSL:5	c.190G>A	p.Asp64Asn	missense	Exon 1 of 12	ENSP00000467899.1	A0A0C4DGQ4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74330

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.68
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.092
Sift	Benign	0.65	T
Sift4G	Benign	0.75	T
Polyphen		0.77	P
Vest4		0.24
MutPred		0.53		Gain of helix (P = 0.1736)
MVP		0.39
MPC		0.022
ClinPred		0.12	T
GERP RS		-0.26
PromoterAI		0.0023	Neutral
Varity_R		0.037
gMVP		0.055
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs796052177; hg19: chr19-56443488; COSMIC: COSV61620687;