16-86520-C-T

Position:

• chr16-86520-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001077350.3(NPRL3):​c.*185G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 609,340 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (2 hom., cov: 34)
  • Exomes 𝑓: 0.0039 (8 hom.)
• Consequence: NPRL3 NM_001077350.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29

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=-0.82).
• BP6: Variant 16-86520-C-T is Benign according to our data. Variant chr16-86520-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1195638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00328 (499/152332) while in subpopulation NFE AF= 0.00444 (302/68010). AF 95% confidence interval is 0.00403. There are 2 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 499 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPRL3	NM_001077350.3	c.*185G>A		3_prime_UTR_variant	14/14	ENST00000611875.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPRL3	ENST00000611875.5	c.*185G>A		3_prime_UTR_variant	14/14	5	NM_001077350.3	P1

Frequencies

GnomAD3 genomes AF: 0.00328 AC: 499 AN: 152214 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00443

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00394 AC: 1799 AN: 457008 Hom.: 8 Cov.: 5 AF XY: 0.00365 AC XY: 869 AN XY: 238230

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.000716

Gnomad4 ASJ exome AF: 0.000972

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.00450

Gnomad4 OTH exome AF: 0.00332

GnomAD4 genome AF: 0.00328 AC: 499 AN: 152332 Hom.: 2 Cov.: 34 AF XY: 0.00364 AC XY: 271 AN XY: 74480

Gnomad4 AFR AF: 0.000793

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.00444

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00360 Hom.: 0

Bravo AF: 0.00248

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs577354419; hg19: chr16-136519;