Variant 19-54938222-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_001405531.1(NLRP7):c.1951C>T(p.Pro651Ser) 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 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NLRP7
NM_001405531.1 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: -0.461

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:):

NCR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 19-54938222-G-A is Pathogenic according to our data. Variant chr19-54938222-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1593.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-54938222-G-A is described in UniProt as null. Variant chr19-54938222-G-A is described in UniProt as null. Variant chr19-54938222-G-A is described in UniProt as null. Variant chr19-54938222-G-A is described in UniProt as null. Variant chr19-54938222-G-A is described in UniProt as null. Variant chr19-54938222-G-A is described in UniProt as null. Variant chr19-54938222-G-A is described in UniProt as null. Variant chr19-54938222-G-A is described in UniProt as null. Variant chr19-54938222-G-A is described in UniProt as null.

BP4

Computational evidence support a benign effect (MetaRNN=0.41765282). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP7	NM_001127255.2 linkuse as main transcript	c.1951C>T	p.Pro651Ser	missense_variant	5/11	ENST00000592784.6	NP_001120727.1
NLRP7	NM_001405531.1 linkuse as main transcript	c.1951C>T	p.Pro651Ser	missense_variant	7/13		NP_001392460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6 linkuse as main transcript	c.1951C>T	p.Pro651Ser	missense_variant	5/11	1	NM_001127255.2	ENSP00000468706	P2	Q8WX94-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Benign

0.16

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Benign

2.8

DANN

Benign

0.79

DEOGEN2

Benign

0.035

T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.064

M_CAP

Benign

0.0017

MetaRNN

Benign

0.42

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N

MutationTaster

Benign

2.4e-12

A;A;A;A;A;A;A

PrimateAI

Benign

0.24

PROVEAN

Benign

0.080

N;.;.;.

REVEL

Benign

0.25

Sift

Benign

0.20

T;.;.;.

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.20

B;B;.;.

Vest4

0.31

MVP

0.21

MPC

0.26

ClinPred

0.081

GERP RS

-0.49

Varity_R

0.11

gMVP

0.083

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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