19-53824059-C-A

Position:

chr19-53824059-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144687.4(NLRP12):c.116G>T(p.Gly39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,613,906 control chromosomes in the GnomAD database, including 39,803 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5246 hom., cov: 31)

Exomes 𝑓: 0.21 ( 34557 hom. )

Consequence

NLRP12
NM_144687.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

NLRP12 (HGNC:22938): (NLR family pyrin domain containing 12) This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

NLRP12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028185844).

BP6

Variant 19-53824059-C-A is Benign according to our data. Variant chr19-53824059-C-A is described in ClinVar as [Benign]. Clinvar id is 262528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-53824059-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP12	NM_144687.4 linkuse as main transcript	c.116G>T	p.Gly39Val	missense_variant	1/10	ENST00000324134.11	NP_653288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP12	ENST00000324134.11 linkuse as main transcript	c.116G>T	p.Gly39Val	missense_variant	1/10	1	NM_144687.4	ENSP00000319377	P4	P59046-1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38404

AN:

151938

Hom.:

5229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.224

AC:

56279

AN:

251390

Hom.:

6733

AF XY:

0.219

AC XY:

29759

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.373

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.178

Gnomad SAS exome

AF:

0.246

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.214

AC:

312531

AN:

1461848

Hom.:

34557

Cov.:

AF XY:

0.214

AC XY:

155607

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.195

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.253

AC:

38462

AN:

152058

Hom.:

5246

Cov.:

AF XY:

0.251

AC XY:

18640

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.368

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.253

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.217

Alfa

AF:

0.208

Hom.:

4416

Bravo

AF:

0.261

TwinsUK

AF:

0.200

AC:

741

ALSPAC

AF:

0.219

AC:

843

ESP6500AA

AF:

0.367

AC:

1619

ESP6500EA

AF:

0.215

AC:

1851

ExAC

AF:

0.229

AC:

27843

Asia WGS

AF:

0.188

AC:

654

AN:

3478

EpiCase

AF:

0.194

EpiControl

AF:

0.188

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Familial cold autoinflammatory syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Familial cold autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;.;.;.;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.59

T;T;T;T;T

MetaRNN

Benign

0.0028

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.8

M;M;M;.;.

MutationTaster

Benign

0.39

P;P;P;P;P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.4

D;D;D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.010

D;D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D;D

Polyphen

0.051

B;.;.;.;.

Vest4

0.19

MPC

0.38

ClinPred

0.035

GERP RS

4.5

Varity_R

0.38

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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