rs73478320

Variant names:

• chr16-110604-T-C
• NM_001077350.3:c.550A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-110604-T-C
• chr16-110604-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077350.3(NPRL3):​c.550A>G​(p.Asn184Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NPRL3 NM_001077350.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11057967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPRL3	NM_001077350.3	c.550A>G	p.Asn184Asp	missense_variant, splice_region_variant	Exon 7 of 14	ENST00000611875.5	NP_001070818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPRL3	ENST00000611875.5	c.550A>G	p.Asn184Asp	missense_variant, splice_region_variant	Exon 7 of 14	5	NM_001077350.3	ENSP00000478273.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454910 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723072

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.039	T;.;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.67	T;T;.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.41	T
REVEL	Benign	0.068
Sift4G	Benign	0.70	T;T;T;.
Polyphen		0.0	B;B;B;.
Vest4		0.053
MutPred		0.47		Gain of disorder (P = 0.0999);.;Gain of disorder (P = 0.0999);.;
MVP		0.13
MPC		0.24
ClinPred		0.091	T
GERP RS		0.58
Varity_R		0.14
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-160602;