NM_176810.2:c.2619-85C>A

Variant names:

• chr19-55902290-G-T
• rs199476256
• NM_176810.2:c.2619-85C>A

Variant summary

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

The NM_176810.2(NLRP13):​c.2619-85C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000204 in 978,682 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: not found (cov: 27)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: NLRP13 NM_176810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 0 publications found

Genes affected

NLRP13 (HGNC:22937): (NLR family pyrin domain containing 13) This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP13	NM_176810.2	c.2619-85C>A		intron_variant	Intron 8 of 10	ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1	c.2619-85C>A		intron_variant	Intron 8 of 11		NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4	c.2619-85C>A		intron_variant	Intron 8 of 10	1	NM_176810.2	ENSP00000343891.3
NLRP13	ENST00000588751.5	c.2619-85C>A		intron_variant	Intron 8 of 11	5		ENSP00000467899.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000204 AC: 2 AN: 978682 Hom.: 0 AF XY: 0.00000408 AC XY: 2 AN XY: 490408

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

African (AFR) AF: 0.0000436 AC: 1 AN: 22940

American (AMR) AF: 0.00 AC: 0 AN: 26740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18020

East Asian (EAS) AF: 0.00 AC: 0 AN: 32760

South Asian (SAS) AF: 0.00 AC: 0 AN: 54888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3234

European-Non Finnish (NFE) AF: 0.00000135 AC: 1 AN: 739704

Other (OTH) AF: 0.00 AC: 0 AN: 42456

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.45
DANN	Benign	0.49
PhyloP100		-0.74

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: rs199476256; hg19: chr19-56413656;