11-278589-C-T

Variant names:

• chr11-278589-C-T
• NM_001276700.2:c.20C>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.20C>T​(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,438,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NLRP6 NM_001276700.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.625
• 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=0.058000237).

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.20C>T	p.Pro7Leu	missense	Exon 1 of 8	NP_001263629.1	P59044-2
	NLRP6	NM_138329.2		c.20C>T	p.Pro7Leu	missense	Exon 1 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.20C>T	p.Pro7Leu	missense	Exon 1 of 8	ENSP00000433617.1	P59044-2
	NLRP6	ENST00000312165.5	TSL:1	c.20C>T	p.Pro7Leu	missense	Exon 1 of 8	ENSP00000309767.4	P59044-1
	ENSG00000293500	ENST00000835501.1		n.275+1228G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1438172 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 714978

African (AFR) AF: 0.00 AC: 0 AN: 32024

American (AMR) AF: 0.00 AC: 0 AN: 41594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25582

East Asian (EAS) AF: 0.00 AC: 0 AN: 36646

South Asian (SAS) AF: 0.00 AC: 0 AN: 83138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1101392

Other (OTH) AF: 0.00 AC: 0 AN: 59446

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.63
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.042
Sift	Benign	0.14	T
Sift4G	Benign	0.11	T
Polyphen		0.063	B
Vest4		0.074
MutPred		0.24		Gain of helix (P = 0.0022)
MVP		0.055
ClinPred		0.096	T
GERP RS		0.076
PromoterAI		-0.0022	Neutral
Varity_R		0.045
gMVP		0.18
Mutation Taster		=96/4	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

hg19: chr11-278589;