Variant rs141755467 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001276700.2(NLRP6):c.669G>C(p.Lys223Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,578,840 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0020 ( 7 hom. )

Consequence

NLRP6
NM_001276700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0490

Variant links:

Genes affected

NLRP6 (HGNC:22944): (NLR family pyrin domain containing 6) The protein encoded by this gene binds arginine-vasopressin and may be involved in the arginine-vasopressin-mediated regulation of renal salt-water balance. The encoded protein also mediates inflammatory responses in the colon to allow recovery from intestinal epithelial damage and protects against tumorigenesis and the development of colitis. Finally, this protein can increase activation of NF-kappa-B, activation of CASP1 through interaction with ASC, and cAMP accumulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

NLRP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010453165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NLRP6	NM_001276700.2 linkuse as main transcript	c.669G>C	p.Lys223Asn	missense_variant	4/8	ENST00000534750.6
NLRP6	NM_138329.2 linkuse as main transcript	c.669G>C	p.Lys223Asn	missense_variant	4/8
NLRP6	XR_930848.2 linkuse as main transcript	n.832G>C		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP6	ENST00000534750.6 linkuse as main transcript	c.669G>C	p.Lys223Asn	missense_variant	4/8	2	NM_001276700.2	A2	P59044-2
NLRP6	ENST00000312165.5 linkuse as main transcript	c.669G>C	p.Lys223Asn	missense_variant	4/8	1		P4	P59044-1

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00112

AC:

221

AN:

197296

Hom.:

AF XY:

0.00110

AC XY:

120

AN XY:

108850

show subpopulations

Gnomad AFR exome

AF:

0.000254

Gnomad AMR exome

AF:

0.000125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000116

Gnomad NFE exome

AF:

0.00240

Gnomad OTH exome

AF:

0.000596

GnomAD4 exome

AF:

0.00196

AC:

2790

AN:

1426528

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1310

AN XY:

708862

show subpopulations

Gnomad4 AFR exome

AF:

0.000250

Gnomad4 AMR exome

AF:

0.000210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.000383

Gnomad4 NFE exome

AF:

0.00243

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152312

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00203

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.00111

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00117

AC:

138

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Mar 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.64

T;T

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.010

T;T

MetaSVM

Uncertain

-0.23

MutationTaster

Benign

0.87

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.46

N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

.;D

Vest4

0.30

MutPred

0.61

Loss of ubiquitination at K223 (P = 0.0233);Loss of ubiquitination at K223 (P = 0.0233);

MVP

0.11

ClinPred

0.055

GERP RS

2.5

Varity_R

0.36

gMVP

0.85

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