rs104895503

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_001127255.2(NLRP7):c.2738A>G(p.Asn913Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000961 in 1,612,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

NLRP7
NM_001127255.2 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2O:1

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

NLRP7 (HGNC:22947): (NLR family pyrin domain containing 7) 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. This gene may act as a feedback regulator of caspase-1-dependent interleukin 1-beta secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

NLRP7 links:

NCR1 (HGNC:6731): (natural cytotoxicity triggering receptor 1) Predicted to be involved in cellular defense response; regulation of natural killer cell mediated cytotoxicity; and signal transduction. Predicted to act upstream of or within defense response to virus and detection of virus. Predicted to be located in cell surface. Predicted to be part of SWI/SNF complex. Predicted to be active in plasma membrane. Biomarker of acquired immunodeficiency syndrome; anogenital venereal wart; hepatitis C; and lymphoproliferative syndrome. [provided by Alliance of Genome Resources, Apr 2022]

NCR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 19-54930571-T-C is Pathogenic according to our data. Variant chr19-54930571-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1588.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in UniProt as null. Variant chr19-54930571-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
NLRP7	NM_001127255.2 link	c.2738A>G	p.Asn913Ser	missense_variant	Exon 9 of 11	NP_001120727.1	Q8WX94-3
NLRP7	NM_001405531.1 link	c.2738A>G	p.Asn913Ser	missense_variant	Exon 11 of 13	NP_001392460.1
NLRP7	NM_139176.4 link	c.2654A>G	p.Asn885Ser	missense_variant	Exon 9 of 11	NP_631915.2	Q8WX94-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6 link	c.2738A>G	p.Asn913Ser	missense_variant	Exon 9 of 11	1		ENSP00000468706.1		Q8WX94-3

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000135

AC:

AN:

251494

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000603

AC:

AN:

1460312

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

726614

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000440

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000465

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hydatidiform mole, recurrent, 1

Pathogenic:2Other:1

Sep 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Oct 12, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;.;T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.073

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.66

D;D;D;D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.5

M;.;M;M;M

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-4.2

D;.;.;.;.

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;.;.;.;.

Sift4G

Uncertain

0.053

T;T;T;T;T

Polyphen

0.99

D;D;D;.;.

Vest4

0.71

MVP

0.57

MPC

0.74

ClinPred

0.15

GERP RS

1.4

Varity_R

0.30

gMVP

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over