rs11248850

Variant names:

• chr16-113599-G-A
• rs11248850
• NM_001077350.3:c.394-824C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-113599-G-A
• chr16-113599-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077350.3(NPRL3):​c.394-824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,076 control chromosomes in the GnomAD database, including 11,892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11892 hom., cov: 32)
• Consequence: NPRL3 NM_001077350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 45 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPRL3	NM_001077350.3	c.394-824C>T		intron_variant	Intron 5 of 13	ENST00000611875.5	NP_001070818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPRL3	ENST00000611875.5	c.394-824C>T		intron_variant	Intron 5 of 13	5	NM_001077350.3	ENSP00000478273.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57215 AN: 151958 Hom.: 11882 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.360

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.376 AC: 57221 AN: 152076 Hom.: 11892 Cov.: 32 AF XY: 0.370 AC XY: 27530 AN XY: 74312

African (AFR) AF: 0.228 AC: 9463 AN: 41506

American (AMR) AF: 0.359 AC: 5480 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1557 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1068 AN: 5162

South Asian (SAS) AF: 0.363 AC: 1746 AN: 4814

European-Finnish (FIN) AF: 0.380 AC: 4013 AN: 10574

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32751 AN: 67958

Other (OTH) AF: 0.356 AC: 750 AN: 2108

Alfa AF: 0.437 Hom.: 35089

Bravo AF: 0.363

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.91
DANN	Benign	0.56
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11248850; hg19: chr16-163598;