Variant 11-7960275-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001391958.1(NLRP10):c.1337T>C(p.Phe446Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00041 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

NLRP10
NM_001391958.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.03

Variant links:

Genes affected

NLRP10 (HGNC:21464): (NLR family pyrin domain containing 10) 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). The protein encoded by this gene belongs to the NALP protein family despite lacking the LRR region. This protein likely plays a regulatory role in the innate immune system. The protein belongs to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. Other experiments indicate that this gene acts as a multifunctional negative regulator of inflammation and apoptosis. [provided by RefSeq, Jul 2008]

NLRP10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP10	NM_001391958.1 linkuse as main transcript	c.1337T>C	p.Phe446Ser	missense_variant	3/3	ENST00000691676.1
NLRP10	NM_176821.4 linkuse as main transcript	c.1337T>C	p.Phe446Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP10	ENST00000691676.1 linkuse as main transcript	c.1337T>C	p.Phe446Ser	missense_variant	3/3		NM_001391958.1	P1
NLRP10	ENST00000328600.3 linkuse as main transcript	c.1337T>C	p.Phe446Ser	missense_variant	2/2	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000426

AC:

107

AN:

251446

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.000739

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000417

AC:

609

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

279

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

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:

0.00103

Gnomad4 NFE exome

AF:

0.000475

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000342

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000393

Hom.:

Bravo

AF:

0.000302

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000544

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.86

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.75

MetaSVM

Uncertain

0.065

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-7.4

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.71

MVP

0.94

MPC

0.49

ClinPred

0.25

GERP RS

3.7

Varity_R

0.81

gMVP

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over