Variant chr16-88726-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBS1BS2

The NM_001077350.3(NPRL3):c.1516A>T(p.Asn506Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,613,032 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

NPRL3
NM_001077350.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.76

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:

NPRL3 (HGNC:):

NPRL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35745215).

BP6

Variant 16-88726-T-A is Benign according to our data. Variant chr16-88726-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 542804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88726-T-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000815 (124/152194) while in subpopulation NFE AF= 0.00148 (101/68040). AF 95% confidence interval is 0.00125. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPRL3	NM_001077350.3 linkuse as main transcript	c.1516A>T	p.Asn506Tyr	missense_variant	13/14	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.1516A>T	p.Asn506Tyr	missense_variant	13/14	5	NM_001077350.3	ENSP00000478273.1		Q12980

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000715

AC:

177

AN:

247476

Hom.:

AF XY:

0.000647

AC XY:

AN XY:

134496

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000932

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

AF:

0.00144

AC:

2099

AN:

1460838

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1007

AN XY:

726578

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00184

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.000815

AC:

124

AN:

152194

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.000959

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.000816

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000230

AC:

ESP6500EA

AF:

0.00199

AC:

ExAC

AF:

0.000635

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00154

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	NPRL3: BS1 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 30, 2021	- -

Epilepsy, familial focal, with variable foci 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

D;D;.

M_CAP

Benign

0.054

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Uncertain

-0.12

PrimateAI

Pathogenic

0.85

REVEL

Uncertain

0.57

Sift4G

Uncertain

0.053

T;T;T

Polyphen

0.99

D;.;D

Vest4

0.89

MVP

0.57

MPC

0.89

ClinPred

0.39

GERP RS

5.5

Varity_R

0.40

gMVP

0.80

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