Variant 16-86889-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001077350.3(NPRL3):c.1545-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,606,368 control chromosomes in the GnomAD database, including 524,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43468 hom., cov: 35)

Exomes 𝑓: 0.81 ( 481051 hom. )

Consequence

NPRL3
NM_001077350.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.820

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-86889-T-C is Benign according to our data. Variant chr16-86889-T-C is described in ClinVar as [Benign]. Clinvar id is 1631816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPRL3	NM_001077350.3 linkuse as main transcript	c.1545-19A>G		intron_variant		ENST00000611875.5	NP_001070818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPRL3	ENST00000611875.5 linkuse as main transcript	c.1545-19A>G		intron_variant		5	NM_001077350.3	ENSP00000478273	P1

Frequencies

GnomAD3 genomes

AF:

0.750

AC:

114021

AN:

152084

Hom.:

43431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.719

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.847

Gnomad EAS

AF:

0.721

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.814

Gnomad OTH

AF:

0.764

GnomAD3 exomes

AF:

0.803

AC:

191126

AN:

237914

Hom.:

77391

AF XY:

0.803

AC XY:

104358

AN XY:

129918

show subpopulations

Gnomad AFR exome

AF:

0.592

Gnomad AMR exome

AF:

0.888

Gnomad ASJ exome

AF:

0.839

Gnomad EAS exome

AF:

0.722

Gnomad SAS exome

AF:

0.833

Gnomad FIN exome

AF:

0.754

Gnomad NFE exome

AF:

0.816

Gnomad OTH exome

AF:

0.806

GnomAD4 exome

AF:

0.812

AC:

1180772

AN:

1454166

Hom.:

481051

Cov.:

AF XY:

0.813

AC XY:

587168

AN XY:

722636

show subpopulations

Gnomad4 AFR exome

AF:

0.582

Gnomad4 AMR exome

AF:

0.879

Gnomad4 ASJ exome

AF:

0.840

Gnomad4 EAS exome

AF:

0.724

Gnomad4 SAS exome

AF:

0.837

Gnomad4 FIN exome

AF:

0.757

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.794

GnomAD4 genome

AF:

0.750

AC:

114107

AN:

152202

Hom.:

43468

Cov.:

AF XY:

0.749

AC XY:

55737

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.606

Gnomad4 AMR

AF:

0.818

Gnomad4 ASJ

AF:

0.847

Gnomad4 EAS

AF:

0.721

Gnomad4 SAS

AF:

0.827

Gnomad4 FIN

AF:

0.748

Gnomad4 NFE

AF:

0.814

Gnomad4 OTH

AF:

0.767

Alfa

AF:

0.767

Hom.:

5522

Bravo

AF:

0.745

Asia WGS

AF:

0.779

AC:

2713

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 96% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 89. Only high quality variants are reported. -

not provided

Benign:1

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.94

DANN

Benign

0.37

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