Variant 16-92716-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001077350.3(NPRL3):c.1041G>A(p.Pro347Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 1,613,346 control chromosomes in the GnomAD database, including 876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 59 hom., cov: 32)

Exomes 𝑓: 0.031 ( 817 hom. )

Consequence

NPRL3
NM_001077350.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.07

Variant links:

Genes affected

NPRL3 (HGNC:14124): (NPR3 like, GATOR1 complex subunit) Contributes to GTPase activator activity. Involved in cellular response to amino acid starvation and negative regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR1 complex. Implicated in focal epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

NPRL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 16-92716-C-T is Benign according to our data. Variant chr16-92716-C-T is described in ClinVar as [Benign]. Clinvar id is 476213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-92716-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0199 (3035/152286) while in subpopulation NFE AF= 0.0355 (2414/68010). AF 95% confidence interval is 0.0343. There are 59 homozygotes in gnomad4. There are 1380 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3035 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPRL3	NM_001077350.3 linkuse as main transcript	c.1041G>A	p.Pro347Pro	synonymous_variant	11/14	ENST00000611875.5	NP_001070818.1	Q12980Q9BTE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPRL3	ENST00000611875.5 linkuse as main transcript	c.1041G>A	p.Pro347Pro	synonymous_variant	11/14	5	NM_001077350.3	ENSP00000478273.1		Q12980

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

3038

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00521

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00933

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0355

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0200

AC:

4945

AN:

247548

Hom.:

AF XY:

0.0207

AC XY:

2786

AN XY:

134460

show subpopulations

Gnomad AFR exome

AF:

0.00601

Gnomad AMR exome

AF:

0.00948

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.0102

Gnomad FIN exome

AF:

0.0112

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0311

AC:

45459

AN:

1461060

Hom.:

817

Cov.:

AF XY:

0.0303

AC XY:

21989

AN XY:

726736

show subpopulations

Gnomad4 AFR exome

AF:

0.00433

Gnomad4 AMR exome

AF:

0.00918

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.000781

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0374

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0199

AC:

3035

AN:

152286

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1380

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00519

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.00933

Gnomad4 NFE

AF:

0.0355

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0270

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0324

EpiControl

AF:

0.0321

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epilepsy, familial focal, with variable foci 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.7

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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