rs370196395

chr16-119150-T-Achr16-119150-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001077350.3(NPRL3):c.294A>T(p.Thr98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T98T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NPRL3 NM_001077350.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.54

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 16-119150-T-A is Benign according to our data. Variant chr16-119150-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 542805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.54 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPRL3	NM_001077350.3	c.294A>T	p.Thr98=	synonymous_variant	4/14	ENST00000611875.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPRL3	ENST00000611875.5	c.294A>T	p.Thr98=	synonymous_variant	4/14	5	NM_001077350.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248046 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134572

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461298 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy, familial focal, with variable foci 3 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 23, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	1.9
Dann	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs370196395; hg19: chr16-169149;