Variant 19-54939626-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001127255.2(NLRP7):c.1193T>G(p.Leu398Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,458,792 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

NLRP7
NM_001127255.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 5.38

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.952

PP5

Variant 19-54939626-A-C is Pathogenic according to our data. Variant chr19-54939626-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 1592.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-54939626-A-C is described in UniProt as null. Variant chr19-54939626-A-C is described in UniProt as null. Variant chr19-54939626-A-C is described in UniProt as null. Variant chr19-54939626-A-C is described in UniProt as null. Variant chr19-54939626-A-C is described in UniProt as null. Variant chr19-54939626-A-C is described in UniProt as null. Variant chr19-54939626-A-C is described in UniProt as null. Variant chr19-54939626-A-C is described in UniProt as null. Variant chr19-54939626-A-C is described in UniProt as null.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
NLRP7	NM_001127255.2 link	c.1193T>G	p.Leu398Arg	missense_variant	4/11	NP_001120727.1	Q8WX94-3
NLRP7	NM_001405531.1 link	c.1193T>G	p.Leu398Arg	missense_variant	6/13	NP_001392460.1
NLRP7	NM_139176.4 link	c.1193T>G	p.Leu398Arg	missense_variant	4/11	NP_631915.2	Q8WX94-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6 link	c.1193T>G	p.Leu398Arg	missense_variant	4/11	1		ENSP00000468706.1		Q8WX94-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000348

AC:

AN:

230008

Hom.:

AF XY:

0.0000554

AC XY:

AN XY:

126356

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000271

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1458792

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725698

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:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000333

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hydatidiform mole, recurrent, 1

Pathogenic:1Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Aug 01, 2009	- -
not provided, no classification provided	literature only	Unité médicale des maladies autoinflammatoires, CHRU Montpellier	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

T;.;T;.;.

Eigen

Benign

0.076

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.95

D;D;D;D;D

MetaSVM

Uncertain

0.18

MutationAssessor

Pathogenic

3.5

M;M;M;M;M

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.1

D;D;.;.;.

REVEL

Uncertain

0.63

Sift

Uncertain

0.0010

D;D;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;.;.

Vest4

0.92

MVP

0.85

MPC

1.1

ClinPred

0.66

GERP RS

1.0

Varity_R

0.62

gMVP

0.88

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