rs11248850

Positions:

• chr16-113599-G-A
• chr16-113599-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NPRL3	NM_001077350.3	c.394-824C>T		intron_variant		ENST00000611875.5	NP_001070818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPRL3	ENST00000611875.5	c.394-824C>T		intron_variant		5	NM_001077350.3	ENSP00000478273	P1

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

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.356

Alfa AF: 0.447 Hom.: 10920

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

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

Other links and lift over

dbSNP: rs11248850; hg19: chr16-163598;