Genetic Variant NLRP6:p.Ser177Leu (chr11-280264-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001276700.2(NLRP6):c.530C>T(p.Ser177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

NLRP6
NM_001276700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17232952).

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>T	p.Ser177Leu	missense	Exon 4 of 8	NP_001263629.1	P59044-2
	NLRP6	NM_138329.2		c.530C>T	p.Ser177Leu	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>T	p.Ser177Leu	missense	Exon 4 of 8	ENSP00000433617.1	P59044-2
NLRP6	ENST00000312165.5	TSL:1	c.530C>T	p.Ser177Leu	missense	Exon 4 of 8	ENSP00000309767.4	P59044-1
ENSG00000293500	ENST00000835501.1		n.-173G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.31e-7

AC:

AN:

1367056

Hom.:

Cov.:

AF XY:

0.00000148

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:

0.0000287

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:

0.00

AC:

AN:

1066858

Other (OTH)

AF:

0.00

AC:

AN:

56394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

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

Uncertain

0.54

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.039

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.50

PhyloP100

-0.46

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.4

REVEL

Benign

0.19

Sift

Benign

0.56

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.26

MVP

0.20

ClinPred

0.31

GERP RS

2.6

Varity_R

0.084

gMVP

0.44

Mutation Taster

=87/13

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