rs114328109

Variant names:

• chr16-86630-C-A
• rs114328109
• NM_001077350.3:c.*75G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-86630-C-A
• chr16-86630-C-G
• chr16-86630-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077350.3(NPRL3):​c.*75G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,278,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: NPRL3 NM_001077350.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial focal epilepsy with variable foci

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.*75G>T		3_prime_UTR	Exon 14 of 14	NP_001070818.1	Q12980
	NPRL3	NM_001243248.2		c.*75G>T		3_prime_UTR	Exon 13 of 13	NP_001230177.1	B7Z6Q0
	NPRL3	NM_001243249.2		c.*75G>T		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.*75G>T		3_prime_UTR	Exon 14 of 14	ENSP00000478273.1	Q12980
	NPRL3	ENST00000399953.7	TSL:1	c.*75G>T		3_prime_UTR	Exon 12 of 12	ENSP00000382834.4	B7Z6Q0
	NPRL3	ENST00000621703.4	TSL:1	n.*1370G>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000477801.1	A0A087WTE2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1278144 Hom.: 0 Cov.: 20 AF XY: 0.00000319 AC XY: 2 AN XY: 626758

African (AFR) AF: 0.00 AC: 0 AN: 29370

American (AMR) AF: 0.00 AC: 0 AN: 31602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21950

East Asian (EAS) AF: 0.00 AC: 0 AN: 34732

South Asian (SAS) AF: 0.00 AC: 0 AN: 71818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3796

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 997360

Other (OTH) AF: 0.00 AC: 0 AN: 53578

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.55
PhyloP100		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs114328109; hg19: chr16-136629;