19-53823938-CC-TT

Variant names:

• chr19-53823938-CC-TT
• NM_144687.4:c.236_237delGGinsAA
• NLRP12 p.Arg79Gln

Variant summary

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

The NM_144687.4(NLRP12):​c.236_237delGGinsAA​(p.Arg79Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R79W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: NLRP12 NM_144687.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451
• Publications: 0 publications found

Genes affected

NLRP12 (HGNC:22938): (NLR family pyrin domain containing 12) This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

NLRP12 Gene-Disease associations (from GenCC):

• familial cold autoinflammatory syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144687.4. 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
	NLRP12	NM_144687.4	MANE Select	c.236_237delGGinsAA	p.Arg79Gln	missense	N/A	NP_653288.1	P59046-1
	NLRP12	NM_001277126.2		c.236_237delGGinsAA	p.Arg79Gln	missense	N/A	NP_001264055.1	P59046-7
	NLRP12	NM_001277129.1		c.236_237delGGinsAA	p.Arg79Gln	missense	N/A	NP_001264058.1	P59046-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP12	ENST00000324134.11	TSL:1 MANE Select	c.236_237delGGinsAA	p.Arg79Gln	missense	N/A	ENSP00000319377.6	P59046-1
	NLRP12	ENST00000391773.8	TSL:1	c.236_237delGGinsAA	p.Arg79Gln	missense	N/A	ENSP00000375653.1	P59046-7
	NLRP12	ENST00000345770.9	TSL:1	c.236_237delGGinsAA	p.Arg79Gln	missense	N/A	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-54327192;