16-130530-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

focal epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
epilepsy, familial focal, with variable foci 3
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial focal epilepsy with variable foci
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NPRL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 476222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

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

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

GnomAD2 exomes

AF:

0.0238

AC:

3727

AN:

156756

AF XY:

0.0230

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 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

African (AFR)

AF:

0.00523

AC:

166

AN:

31718

American (AMR)

AF:

0.0379

AC:

1363

AN:

35922

Ashkenazi Jewish (ASJ)

AF:

0.00376

AC:

AN:

25288

East Asian (EAS)

AF:

0.0726

AC:

2610

AN:

35930

South Asian (SAS)

AF:

0.0305

AC:

2419

AN:

79380

European-Finnish (FIN)

AF:

0.0315

AC:

1510

AN:

47930

Middle Eastern (MID)

AF:

0.0212

AC:

120

AN:

5666

European-Non Finnish (NFE)

AF:

0.0138

AC:

14905

AN:

1079720

Other (OTH)

AF:

0.0174

AC:

1012

AN:

58096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1157

2313

3470

4626

5783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

642

1284

1926

2568

3210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0163

AC:

2478

AN:

152356

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1335

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00495

AC:

206

AN:

41588

American (AMR)

AF:

0.0293

AC:

448

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.0671

AC:

348

AN:

5184

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4834

European-Finnish (FIN)

AF:

0.0404

AC:

429

AN:

10610

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0123

AC:

839

AN:

68042

Other (OTH)

AF:

0.0246

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

128

256

384

512

640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0147

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

AlphaMissense

Benign

0.086

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.94

(source)

DANN

Benign

0.93

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=296/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over