11-279335-C-T

Variant names:

• chr11-279335-C-T
• rs569717686
• NM_001276700.2:c.38C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001276700.2(NLRP6):​c.38C>T​(p.Pro13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. P13R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NLRP6 NM_001276700.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 0 publications found

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]

ENSG00000293500 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03667301).

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>T	p.Pro13Leu	missense	Exon 2 of 8	NP_001263629.1	P59044-2
	NLRP6	NM_138329.2		c.38C>T	p.Pro13Leu	missense	Exon 2 of 8	NP_612202.2	P59044-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP6	ENST00000534750.6	TSL:2 MANE Select	c.38C>T	p.Pro13Leu	missense	Exon 2 of 8	ENSP00000433617.1	P59044-2
	NLRP6	ENST00000312165.5	TSL:1	c.38C>T	p.Pro13Leu	missense	Exon 2 of 8	ENSP00000309767.4	P59044-1
	NLRP6	ENST00000527946.1	TSL:4	n.277C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152078 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1137540 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 544746

African (AFR) AF: 0.00 AC: 0 AN: 23138

American (AMR) AF: 0.00 AC: 0 AN: 8486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15410

East Asian (EAS) AF: 0.00 AC: 0 AN: 26576

South Asian (SAS) AF: 0.00 AC: 0 AN: 38238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3052

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 950414

Other (OTH) AF: 0.00 AC: 0 AN: 45972

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152078 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.074
DANN	Benign	0.80
DEOGEN2	Benign	0.037	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.88	T
PhyloP100		-2.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.11
Sift	Benign	0.67	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.29		Loss of loop (P = 0.0073)
MVP		0.030
ClinPred		0.036	T
GERP RS		-6.8
Varity_R		0.022
gMVP		0.15
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs569717686; hg19: chr11-279335;