Variant 19-56003968-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_153447.4(NLRP5):c.315C>T(p.Asn105Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,728 control chromosomes in the GnomAD database, including 16,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2106 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14148 hom. )

Consequence

NLRP5
NM_153447.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.73

Variant links:

Genes affected

NLRP5 (HGNC:21269): (NLR family pyrin domain containing 5) 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). Expression of this gene is restricted to the oocyte. A mouse gene that encodes a maternal oocyte protein, similar to this encoded protein, is required for normal early embryogenesis. [provided by RefSeq, Jul 2008]

NLRP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-56003968-C-T is Benign according to our data. Variant chr19-56003968-C-T is described in ClinVar as [Benign]. Clinvar id is 3059251.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP5	NM_153447.4 link	c.315C>T	p.Asn105Asn	synonymous_variant	2/15	ENST00000390649.8	NP_703148.4	P59047

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP5	ENST00000390649.8 link	c.315C>T	p.Asn105Asn	synonymous_variant	2/15	1	NM_153447.4	ENSP00000375063.3		P59047
NLRP5	ENST00000597673.1 link	n.234C>T		non_coding_transcript_exon_variant	1/5	5		ENSP00000471494.1		M0R0W4

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23596

AN:

151966

Hom.:

2101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.0749

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.134

GnomAD3 exomes

AF:

0.166

AC:

41265

AN:

249166

Hom.:

4261

AF XY:

0.157

AC XY:

21200

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.284

Gnomad ASJ exome

AF:

0.0651

Gnomad EAS exome

AF:

0.310

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.129

AC:

187864

AN:

1461644

Hom.:

14148

Cov.:

AF XY:

0.127

AC XY:

92410

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.0661

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.155

AC:

23621

AN:

152084

Hom.:

2106

Cov.:

AF XY:

0.160

AC XY:

11891

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.0749

Gnomad4 EAS

AF:

0.314

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.116

Hom.:

2670

Bravo

AF:

0.157

Asia WGS

AF:

0.232

AC:

807

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.105

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NLRP5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 05, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.91

DANN

Benign

0.52

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over