16-86637-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001077350.3(NPRL3):c.*68T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,447,954 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (67 hom., cov: 34)
  • Exomes 𝑓: 0.0018 (41 hom.)
• Consequence: NPRL3 NM_001077350.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.162

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-86637-A-C is Benign according to our data. Variant chr16-86637-A-C is described in ClinVar as [Benign]. Clinvar id is 1240682.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPRL3	NM_001077350.3	c.*68T>G		3_prime_UTR_variant	14/14	ENST00000611875.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPRL3	ENST00000611875.5	c.*68T>G		3_prime_UTR_variant	14/14	5	NM_001077350.3	P1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2423 AN: 151568 Hom.: 67 Cov.: 34

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00754

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000575

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00183 AC: 2375 AN: 1296268 Hom.: 41 Cov.: 21 AF XY: 0.00169 AC XY: 1077 AN XY: 635554

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.00504

Gnomad4 ASJ exome AF: 0.0000890

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000341

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000412

Gnomad4 OTH exome AF: 0.00460

GnomAD4 genome AF: 0.0161 AC: 2437 AN: 151686 Hom.: 67 Cov.: 34 AF XY: 0.0156 AC XY: 1155 AN XY: 74124

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.00753

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000575

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.0135 Hom.: 5

Bravo AF: 0.0189

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.4
Dann	Benign	0.39

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: rs10451206; hg19: chr16-136636;