rs10451206

Variant names:

• chr16-86637-A-C
• rs10451206
• NM_001077350.3:c.*68T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-86637-A-C
• chr16-86637-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.162
• Publications: 2 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.86).
• BP6: Variant 16-86637-A-C is Benign according to our data. Variant chr16-86637-A-C is described in ClinVar as Benign. ClinVar VariationId is 1240682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

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.*68T>G		3_prime_UTR	Exon 14 of 14	NP_001070818.1	Q12980
	NPRL3	NM_001243248.2		c.*68T>G		3_prime_UTR	Exon 13 of 13	NP_001230177.1	B7Z6Q0
	NPRL3	NM_001243249.2		c.*68T>G		3_prime_UTR	Exon 12 of 12	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.*68T>G		3_prime_UTR	Exon 14 of 14	ENSP00000478273.1	Q12980
	NPRL3	ENST00000399953.7	TSL:1	c.*68T>G		3_prime_UTR	Exon 12 of 12	ENSP00000382834.4	B7Z6Q0
	NPRL3	ENST00000621703.4	TSL:1	n.*1363T>G		non_coding_transcript_exon	Exon 11 of 11	ENSP00000477801.1	A0A087WTE2

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

African (AFR) AF: 0.0500 AC: 1485 AN: 29700

American (AMR) AF: 0.00504 AC: 162 AN: 32154

Ashkenazi Jewish (ASJ) AF: 0.0000890 AC: 2 AN: 22466

East Asian (EAS) AF: 0.00 AC: 0 AN: 34800

South Asian (SAS) AF: 0.000341 AC: 25 AN: 73236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34752

Middle Eastern (MID) AF: 0.00902 AC: 35 AN: 3882

European-Non Finnish (NFE) AF: 0.000412 AC: 417 AN: 1011132

Other (OTH) AF: 0.00460 AC: 249 AN: 54146

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

African (AFR) AF: 0.0545 AC: 2252 AN: 41302

American (AMR) AF: 0.00753 AC: 115 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000575 AC: 39 AN: 67854

Other (OTH) AF: 0.0138 AC: 29 AN: 2108

Alfa AF: 0.0142 Hom.: 5

Bravo AF: 0.0189

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		-0.16
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: rs10451206; hg19: chr16-136636;