3-50347546-AC-A

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]

Genome browser will be placed here

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 HGVSp Effect #exon/exons MANE UniProt
NPRL2NM_006545.5 linkuse as main transcriptc.*59del 3_prime_UTR_variant 11/11 ENST00000232501.8
NPRL2XM_011533288.4 linkuse as main transcriptc.*59del 3_prime_UTR_variant 10/10
NPRL2XM_017005556.3 linkuse as main transcriptc.*59del 3_prime_UTR_variant 9/9
NPRL2XM_047447310.1 linkuse as main transcriptc.*59del 3_prime_UTR_variant 11/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPRL2ENST00000232501.8 linkuse as main transcriptc.*59del 3_prime_UTR_variant 11/111 NM_006545.5 P1Q8WTW4-1

Frequencies

GnomAD3 genomes
AF:
0.0872
AC:
13238
AN:
151852
Hom.:
1897
Cov.:
31
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.:
28
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.:
31
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.:
4
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 submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJul 31, 2024This 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 submitterclinical testingGeneDxMay 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.

Other links and lift over

dbSNP: rs34963734; hg19: chr3-50384977; COSMIC: COSV51602072; COSMIC: COSV51602072; API