Variant chr3-50347546-AC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006545.5(NPRL2):c.*59del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 1,596,450 control chromosomes in the GnomAD database, including 12,239 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 1898 hom., cov: 31)

Exomes 𝑓: 0.036 ( 10341 hom. )

Consequence

NPRL2
NM_006545.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150

Variant links:

Genes affected

NPRL2 (HGNC:24969): (NPR2 like, GATOR1 complex subunit) Enables protein kinase activity. Contributes to GTPase activator activity. Involved in cellular response to amino acid starvation; negative regulation of TOR signaling; and negative regulation of kinase activity. Located in lysosomal membrane. Part of GATOR1 complex. Implicated in focal epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

NPRL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-50347546-AC-A is Benign according to our data. Variant chr3-50347546-AC-A is described in ClinVar as [Benign]. Clinvar id is 1249338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
NPRL2	NM_006545.5 linkuse as main transcript	c.*59del	3_prime_UTR_variant	11/11	ENST00000232501.8
NPRL2	XM_011533288.4 linkuse as main transcript	c.*59del	3_prime_UTR_variant	10/10
NPRL2	XM_017005556.3 linkuse as main transcript	c.*59del	3_prime_UTR_variant	9/9
NPRL2	XM_047447310.1 linkuse as main transcript	c.*59del	3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPRL2	ENST00000232501.8 linkuse as main transcript	c.*59del		3_prime_UTR_variant	11/11	1	NM_006545.5	P1	Q8WTW4-1

Frequencies

GnomAD3 genomes

AF:

0.0872

AC:

13238

AN:

151852

Hom.:

1897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.597

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0467

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00349

Gnomad OTH

AF:

0.0791

GnomAD4 exome

AF:

0.0355

AC:

51304

AN:

1444480

Hom.:

10341

Cov.:

AF XY:

0.0322

AC XY:

23192

AN XY:

719758

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.386

Gnomad4 ASJ exome

AF:

0.00419

Gnomad4 EAS exome

AF:

0.534

Gnomad4 SAS exome

AF:

0.00995

Gnomad4 FIN exome

AF:

0.0440

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.0534

GnomAD4 genome

AF:

0.0873

AC:

13263

AN:

151970

Hom.:

1898

Cov.:

AF XY:

0.0936

AC XY:

6953

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.260

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.598

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.0467

Gnomad4 NFE

AF:

0.00349

Gnomad4 OTH

AF:

0.0797

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.110

Asia WGS

AF:

0.203

AC:

704

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 45% 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: 42. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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