rs141755467
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001276700.2(NLRP6):āc.669G>Cā(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 (ā ).
Frequency
Genomes: š 0.0011 ( 0 hom., cov: 34)
Exomes š: 0.0020 ( 7 hom. )
Consequence
NLRP6
NM_001276700.2 missense
NM_001276700.2 missense
Scores
2
6
10
Clinical Significance
Conservation
PhyloP100: -0.0490
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 Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.010453165).
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLRP6 | NM_001276700.2 | c.669G>C | p.Lys223Asn | missense_variant | 4/8 | ENST00000534750.6 | |
NLRP6 | NM_138329.2 | c.669G>C | p.Lys223Asn | missense_variant | 4/8 | ||
NLRP6 | XR_930848.2 | 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 | c.669G>C | p.Lys223Asn | missense_variant | 4/8 | 2 | NM_001276700.2 | A2 | |
NLRP6 | ENST00000312165.5 | c.669G>C | p.Lys223Asn | missense_variant | 4/8 | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00109 AC: 166AN: 152204Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00112 AC: 221AN: 197296Hom.: 1 AF XY: 0.00110 AC XY: 120AN XY: 108850
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GnomAD4 exome AF: 0.00196 AC: 2790AN: 1426528Hom.: 7 Cov.: 70 AF XY: 0.00185 AC XY: 1310AN XY: 708862
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GnomAD4 genome AF: 0.00109 AC: 166AN: 152312Hom.: 0 Cov.: 34 AF XY: 0.00105 AC XY: 78AN XY: 74492
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
Loss of ubiquitination at K223 (P = 0.0233);Loss of ubiquitination at K223 (P = 0.0233);
MVP
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at