Variant 19-56003965-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_153447.4(NLRP5):c.312C>T(p.Ala104Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 1,613,864 control chromosomes in the GnomAD database, including 1,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.031 ( 120 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1503 hom. )

Consequence

NLRP5
NM_153447.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0550

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-56003965-C-T is Benign according to our data. Variant chr19-56003965-C-T is described in ClinVar as [Benign]. Clinvar id is 3056195.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.055 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0309 (4704/152188) while in subpopulation NFE AF= 0.05 (3401/67998). AF 95% confidence interval is 0.0486. There are 120 homozygotes in gnomad4. There are 2111 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 120 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP5	NM_153447.4 link	c.312C>T	p.Ala104Ala	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.312C>T	p.Ala104Ala	synonymous_variant	2/15	1	NM_153447.4	ENSP00000375063.3		P59047
NLRP5	ENST00000597673.1 link	n.231C>T		non_coding_transcript_exon_variant	1/5	5		ENSP00000471494.1		M0R0W4

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4706

AN:

152070

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00857

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0314

Gnomad ASJ

AF:

0.0525

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00953

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0500

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0309

AC:

7694

AN:

249254

Hom.:

171

AF XY:

0.0314

AC XY:

4246

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00749

Gnomad AMR exome

AF:

0.0226

Gnomad ASJ exome

AF:

0.0535

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0108

Gnomad FIN exome

AF:

0.0154

Gnomad NFE exome

AF:

0.0474

Gnomad OTH exome

AF:

0.0405

GnomAD4 exome

AF:

0.0416

AC:

60784

AN:

1461676

Hom.:

1503

Cov.:

AF XY:

0.0412

AC XY:

29983

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00669

Gnomad4 AMR exome

AF:

0.0238

Gnomad4 ASJ exome

AF:

0.0551

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00999

Gnomad4 FIN exome

AF:

0.0158

Gnomad4 NFE exome

AF:

0.0484

Gnomad4 OTH exome

AF:

0.0376

GnomAD4 genome

AF:

0.0309

AC:

4704

AN:

152188

Hom.:

120

Cov.:

AF XY:

0.0284

AC XY:

2111

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00855

Gnomad4 AMR

AF:

0.0314

Gnomad4 ASJ

AF:

0.0525

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00933

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.0500

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0423

Hom.:

Bravo

AF:

0.0313

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0567

EpiControl

AF:

0.0559

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

Mar 06, 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

-0.84

CADD

Benign

3.2

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