11-279352-C-T

Variant names:

• chr11-279352-C-T
• rs1181620644
• NM_001276700.2:c.55C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001276700.2(NLRP6):​c.55C>T​(p.Arg19Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000875 in 1,142,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R19G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: NLRP6 NM_001276700.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.55C>T	p.Arg19Cys	missense	Exon 2 of 8	NP_001263629.1	P59044-2
	NLRP6	NM_138329.2		c.55C>T	p.Arg19Cys	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.55C>T	p.Arg19Cys	missense	Exon 2 of 8	ENSP00000433617.1	P59044-2
	NLRP6	ENST00000312165.5	TSL:1	c.55C>T	p.Arg19Cys	missense	Exon 2 of 8	ENSP00000309767.4	P59044-1
	NLRP6	ENST00000527946.1	TSL:4	n.294C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.75e-7 AC: 1 AN: 1142508 Hom.: 0 Cov.: 35 AF XY: 0.00000183 AC XY: 1 AN XY: 547628

African (AFR) AF: 0.00 AC: 0 AN: 23176

American (AMR) AF: 0.00 AC: 0 AN: 8538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15548

East Asian (EAS) AF: 0.00 AC: 0 AN: 26628

South Asian (SAS) AF: 0.00 AC: 0 AN: 39542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3064

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 952970

Other (OTH) AF: 0.00 AC: 0 AN: 46240

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.0060	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.080
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.57	T
PhyloP100		-0.25
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.39
MutPred		0.66		Loss of disorder (P = 0.0475)
MVP		0.40
ClinPred		0.98	D
GERP RS		2.7
Varity_R		0.45
gMVP		0.47
Mutation Taster		=31/69	disease causing

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: rs1181620644; hg19: chr11-279352; COSMIC: COSV56460258;