chr11-279335-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 13/19 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

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.29
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022860467).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NLRP6NM_001276700.2 linkc.38C>G p.Pro13Arg missense_variant Exon 2 of 8 ENST00000534750.6 NP_001263629.1 P59044-2
NLRP6NM_138329.2 linkc.38C>G p.Pro13Arg missense_variant Exon 2 of 8 NP_612202.2 P59044-1
NLRP6XR_930848.2 linkn.201C>G non_coding_transcript_exon_variant Exon 2 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NLRP6ENST00000534750.6 linkc.38C>G p.Pro13Arg missense_variant Exon 2 of 8 2 NM_001276700.2 ENSP00000433617.1 P59044-2
NLRP6ENST00000312165.5 linkc.38C>G p.Pro13Arg missense_variant Exon 2 of 8 1 ENSP00000309767.4 P59044-1
NLRP6ENST00000527946.1 linkn.277C>G non_coding_transcript_exon_variant Exon 1 of 2 4

Frequencies

GnomAD3 genomes
AF:
0.000592
AC:
90
AN:
152078
Hom.:
0
Cov.:
33
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
GnomAD4 exome
AF:
0.0000721
AC:
82
AN:
1137540
Hom.:
1
Cov.:
35
AF XY:
0.0000771
AC XY:
42
AN XY:
544746
show subpopulations
Gnomad4 AFR exome
AF:
0.00246
Gnomad4 AMR exome
AF:
0.000354
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000523
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000618
AC:
94
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.000538
AC XY:
40
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.00207
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000744
ExAC
AF:
0.000126
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.38C>G (p.P13R) alteration is located in exon 2 (coding exon 2) of the NLRP6 gene. This alteration results from a C to G substitution at nucleotide position 38, causing the proline (P) at amino acid position 13 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
0.084
DANN
Benign
0.60
DEOGEN2
Benign
0.083
.;T
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.32
T;T
M_CAP
Uncertain
0.087
D
MetaRNN
Benign
0.023
T;T
MetaSVM
Benign
-0.92
T
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.16
Sift
Benign
0.38
T;T
Sift4G
Benign
0.15
T;T
Polyphen
0.0030
.;B
Vest4
0.052
MutPred
0.23
Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);
MVP
0.040
ClinPred
0.23
T
GERP RS
-6.8
Varity_R
0.035
gMVP
0.15

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.

Other links and lift over

dbSNP: rs569717686; hg19: chr11-279335; API