Variant 19-55947913-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_176811.2(NLRP8):c.11T>C(p.Val4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NLRP8
NM_176811.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.248

Variant links:

Genes affected

NLRP8 (HGNC:22940): (NLR family pyrin domain containing 8) This gene encodes a member of the nucleotide-binding oligomerization domain/ leucine rich repeat/ pyrin domain containing (NLRP) subfamily, which belongs to the Nod-like receptor family of proteins. NLRP genes play roles in the mammalian innate immune system through inflammasome formation and activation of caspases. In addition, NLRP genes have been found to function during mammalian reproduction. Consistent with a function during human preimplantation development, this gene is expressed at high levels in oocytes with decreased levels in embryos. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

NLRP8 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051377267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP8	NM_176811.2 linkuse as main transcript	c.11T>C	p.Val4Ala	missense_variant	1/10	ENST00000291971.7	NP_789781.2	Q86W28-1
NLRP8	NM_001317000.1 linkuse as main transcript	c.11T>C	p.Val4Ala	missense_variant	1/10		NP_001303929.1	Q86W28-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP8	ENST00000291971.7 linkuse as main transcript	c.11T>C	p.Val4Ala	missense_variant	1/10	1	NM_176811.2	ENSP00000291971.3		Q86W28-1
NLRP8	ENST00000590542.1 linkuse as main transcript	c.11T>C	p.Val4Ala	missense_variant	1/10	1		ENSP00000468121.1		Q86W28-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458416

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725078

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.11T>C (p.V4A) alteration is located in exon 1 (coding exon 1) of the NLRP8 gene. This alteration results from a T to C substitution at nucleotide position 11, causing the valine (V) at amino acid position 4 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.9

DANN

Benign

0.40

DEOGEN2

Benign

0.00098

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.28

N;.

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.094

T;T

Polyphen

0.0020

B;B

Vest4

0.15

MutPred

0.063

Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);

MVP

0.24

MPC

0.11

ClinPred

0.070

GERP RS

-3.7

Varity_R

0.074

gMVP

0.040

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over