dbSNP rs75187722: NPRL3:p.Gly60Gly (chr16-130530-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001077350.3(NPRL3):c.180C>T(p.Gly60Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,552,006 control chromosomes in the GnomAD database, including 414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 50 hom., cov: 33)

Exomes 𝑓: 0.017 ( 364 hom. )

Consequence

NPRL3
NM_001077350.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.84

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 16-130530-G-A is Benign according to our data. Variant chr16-130530-G-A is described in ClinVar as [Benign]. Clinvar id is 476222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-130530-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPRL3	NM_001077350.3 link	c.180C>T	p.Gly60Gly	synonymous_variant	Exon 3 of 14	ENST00000611875.5	NP_001070818.1	Q12980Q9BTE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPRL3	ENST00000611875.5 link	c.180C>T	p.Gly60Gly	synonymous_variant	Exon 3 of 14	5	NM_001077350.3	ENSP00000478273.1		Q12980

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2448

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00492

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0666

Gnomad SAS

AF:

0.0287

Gnomad FIN

AF:

0.0404

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0181

GnomAD3 exomes

AF:

0.0238

AC:

3727

AN:

156756

Hom.:

AF XY:

0.0230

AC XY:

1918

AN XY:

83308

show subpopulations

Gnomad AFR exome

AF:

0.00468

Gnomad AMR exome

AF:

0.0384

Gnomad ASJ exome

AF:

0.00393

Gnomad EAS exome

AF:

0.0647

Gnomad SAS exome

AF:

0.0301

Gnomad FIN exome

AF:

0.0313

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0173

AC:

24200

AN:

1399650

Hom.:

364

Cov.:

AF XY:

0.0177

AC XY:

12212

AN XY:

690636

show subpopulations

Gnomad4 AFR exome

AF:

0.00523

Gnomad4 AMR exome

AF:

0.0379

Gnomad4 ASJ exome

AF:

0.00376

Gnomad4 EAS exome

AF:

0.0726

Gnomad4 SAS exome

AF:

0.0305

Gnomad4 FIN exome

AF:

0.0315

Gnomad4 NFE exome

AF:

0.0138

Gnomad4 OTH exome

AF:

0.0174

GnomAD4 genome

AF:

0.0163

AC:

2478

AN:

152356

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1335

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00495

Gnomad4 AMR

AF:

0.0293

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0671

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.0404

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0150

Asia WGS

AF:

0.0850

AC:

296

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NPRL3-related disorder

Benign:1

Apr 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Epilepsy, familial focal, with variable foci 3

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.94

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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