Genetic Variant NLRP6:p.Pro13Arg (chr11-279335-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001276700.2(NLRP6):c.38C>G(p.Pro13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,289,728 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000072 ( 1 hom. )

Consequence

NLRP6
NM_001276700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.29

Publications

0 publications found

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:

ENSG00000293500 (HGNC:):

ENSG00000293500 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022860467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP6	NM_001276700.2	MANE Select	c.38C>G	p.Pro13Arg	missense	Exon 2 of 8	NP_001263629.1	P59044-2
	NLRP6	NM_138329.2		c.38C>G	p.Pro13Arg	missense	Exon 2 of 8	NP_612202.2	P59044-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLRP6	ENST00000534750.6	TSL:2 MANE Select	c.38C>G	p.Pro13Arg	missense	Exon 2 of 8	ENSP00000433617.1	P59044-2
NLRP6	ENST00000312165.5	TSL:1	c.38C>G	p.Pro13Arg	missense	Exon 2 of 8	ENSP00000309767.4	P59044-1
NLRP6	ENST00000527946.1	TSL:4	n.277C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

570

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000721

AC:

AN:

1137540

Hom.:

Cov.:

AF XY:

0.0000771

AC XY:

AN XY:

544746

show subpopulations

African (AFR)

AF:

0.00246

AC:

AN:

23138

American (AMR)

AF:

0.000354

AC:

AN:

8486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15410

East Asian (EAS)

AF:

0.00

AC:

AN:

26576

South Asian (SAS)

AF:

0.0000523

AC:

AN:

38238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26254

Middle Eastern (MID)

AF:

0.00131

AC:

AN:

3052

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

950414

Other (OTH)

AF:

0.000348

AC:

AN:

45972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000618

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41550

American (AMR)

AF:

0.000523

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000744

ExAC

AF:

0.000126

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.084

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.083

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.92

PhyloP100

-2.3

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

REVEL

Benign

0.16

Sift

Benign

0.38

Sift4G

Benign

0.15

Polyphen

0.0030

Vest4

0.052

MutPred

0.23

Gain of helix (P = 6e-04)

MVP

0.040

ClinPred

0.23

GERP RS

-6.8

Varity_R

0.035

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over