rs117823353

Variant names:

• chr11-7039717-C-G
• NM_176822.4:c.293C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-7039717-C-G
• chr11-7039717-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_176822.4(NLRP14):​c.293C>G​(p.Ser98Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 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. S98L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NLRP14 NM_176822.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924

Genes affected

NLRP14 (HGNC:22939): (NLR family pyrin domain containing 14) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). This protein may play a regulatory role in the innate immune system as similar family members belong to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP14	NM_176822.4	c.293C>G	p.Ser98Trp	missense_variant	Exon 3 of 12	ENST00000299481.5	NP_789792.1
NLRP14	XM_011520044.2	c.293C>G	p.Ser98Trp	missense_variant	Exon 3 of 11		XP_011518346.1
NLRP14	XM_047426867.1	c.293C>G	p.Ser98Trp	missense_variant	Exon 3 of 11		XP_047282823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP14	ENST00000299481.5	c.293C>G	p.Ser98Trp	missense_variant	Exon 3 of 12	5	NM_176822.4	ENSP00000299481.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460586 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726694

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.17
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.97	D
Vest4		0.37
MutPred		0.37		Loss of disorder (P = 0.024);
MVP		0.67
MPC		0.082
ClinPred		0.22	T
GERP RS		1.5
Varity_R		0.14
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: -3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-7060948;