Genetic Variant NLRP6:p.Ser177Trp (chr11-280264-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001276700.2(NLRP6):c.530C>G(p.Ser177Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,367,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S177L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NLRP6
NM_001276700.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.460

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4238996).

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.530C>G	p.Ser177Trp	missense	Exon 4 of 8	NP_001263629.1	P59044-2
	NLRP6	NM_138329.2		c.530C>G	p.Ser177Trp	missense	Exon 4 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.530C>G	p.Ser177Trp	missense	Exon 4 of 8	ENSP00000433617.1	P59044-2
NLRP6	ENST00000312165.5	TSL:1	c.530C>G	p.Ser177Trp	missense	Exon 4 of 8	ENSP00000309767.4	P59044-1
ENSG00000293500	ENST00000835501.1		n.-173G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1367056

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

673800

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28748

American (AMR)

AF:

0.00

AC:

AN:

29554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23382

East Asian (EAS)

AF:

0.00

AC:

AN:

34786

South Asian (SAS)

AF:

0.00

AC:

AN:

76094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4802

European-Non Finnish (NFE)

AF:

0.0000141

AC:

AN:

1066858

Other (OTH)

AF:

0.00

AC:

AN:

56394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.43

PhyloP100

-0.46

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.34

Sift

Benign

0.24

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.51

MutPred

0.30

Loss of phosphorylation at S177 (P = 0.0057)

MVP

0.27

ClinPred

0.35

GERP RS

2.6

Varity_R

0.096

gMVP

0.47

Mutation Taster

=84/16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over