rs147148279

Variant names:

• chr16-88680-G-A
• rs147148279
• NM_001077350.3:c.1544+18C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88680-G-A
• chr16-88680-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001077350.3(NPRL3):​c.1544+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000748 in 1,595,064 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (2 hom.)
• Consequence: NPRL3 NM_001077350.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.39
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial focal epilepsy with variable foci

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-88680-G-A is Benign according to our data. Variant chr16-88680-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00389 (592/152304) while in subpopulation AFR AF = 0.0133 (554/41548). AF 95% confidence interval is 0.0124. There are 4 homozygotes in GnomAd4. There are 279 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 592 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077350.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPRL3	NM_001077350.3	MANE Select	c.1544+18C>T		intron	N/A	NP_001070818.1	Q12980
	NPRL3	NM_001243248.2		c.1469+18C>T		intron	N/A	NP_001230177.1	B7Z6Q0
	NPRL3	NM_001243249.2		c.1469+18C>T		intron	N/A	NP_001230178.1	B7Z6Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPRL3	ENST00000611875.5	TSL:5 MANE Select	c.1544+18C>T		intron	N/A	ENSP00000478273.1	Q12980
	NPRL3	ENST00000399953.7	TSL:1	c.1469+18C>T		intron	N/A	ENSP00000382834.4	B7Z6Q0
	NPRL3	ENST00000621703.4	TSL:1	n.*1129+18C>T		intron	N/A	ENSP00000477801.1	A0A087WTE2

Frequencies

GnomAD3 genomes AF: 0.00389 AC: 592 AN: 152186 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.000936 AC: 224 AN: 239282 AF XY: 0.000754

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.000918

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000173

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000371

Gnomad OTH exome AF: 0.000341

GnomAD4 exome AF: 0.000417 AC: 601 AN: 1442760 Hom.: 2 Cov.: 31 AF XY: 0.000377 AC XY: 269 AN XY: 713888

African (AFR) AF: 0.0135 AC: 447 AN: 33078

American (AMR) AF: 0.000909 AC: 40 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.000334 AC: 13 AN: 38900

South Asian (SAS) AF: 0.0000588 AC: 5 AN: 85038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52850

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5688

European-Non Finnish (NFE) AF: 0.0000437 AC: 48 AN: 1097886

Other (OTH) AF: 0.000757 AC: 45 AN: 59480

GnomAD4 genome AF: 0.00389 AC: 592 AN: 152304 Hom.: 4 Cov.: 33 AF XY: 0.00375 AC XY: 279 AN XY: 74476

African (AFR) AF: 0.0133 AC: 554 AN: 41548

American (AMR) AF: 0.00111 AC: 17 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68032

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00167 Hom.: 0

Bravo AF: 0.00452

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Epilepsy, familial focal, with variable foci 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.41
DANN	Benign	0.40
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs147148279; hg19: chr16-138679;