NM_144687.4:c.*205G>C

Variant names:

• chr19-53793844-C-G
• rs564145946
• NM_144687.4:c.*205G>C

Variant summary

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

The NM_144687.4(NLRP12):​c.*205G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 645,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: NLRP12 NM_144687.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• 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: 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 (BayesDel_noAF=-0.94).

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.*205G>C		3_prime_UTR	Exon 10 of 10	NP_653288.1	P59046-1
	NLRP12	NM_001277126.2		c.*205G>C		3_prime_UTR	Exon 10 of 10	NP_001264055.1	P59046-7
	NLRP12	NM_001277129.1		c.*205G>C		3_prime_UTR	Exon 9 of 9	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.*205G>C		3_prime_UTR	Exon 10 of 10	ENSP00000319377.6	P59046-1
	NLRP12	ENST00000391773.8	TSL:1	c.*205G>C		3_prime_UTR	Exon 10 of 10	ENSP00000375653.1	P59046-7
	NLRP12	ENST00000345770.9	TSL:1	c.*205G>C		3_prime_UTR	Exon 9 of 9	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151960 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000203 AC: 1 AN: 493544 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 263480

African (AFR) AF: 0.00 AC: 0 AN: 14308

American (AMR) AF: 0.0000344 AC: 1 AN: 29090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16326

East Asian (EAS) AF: 0.00 AC: 0 AN: 31176

South Asian (SAS) AF: 0.00 AC: 0 AN: 53346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2148

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 287574

Other (OTH) AF: 0.00 AC: 0 AN: 27810

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151960 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74218

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000242 AC: 1 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.99
DANN	Benign	0.27
PhyloP100		-0.77

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: rs564145946; hg19: chr19-54297098;