rs200322306

Variant names:

• chr16-2471958-G-A
• rs200322306
• NM_006181.3:c.257G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-2471958-G-A
• chr16-2471958-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006181.3(NTN3):​c.257G>A​(p.Gly86Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,571,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: NTN3 NM_006181.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.397
• Publications: 0 publications found

Genes affected

NTN3 (HGNC:8030): (netrin 3) Predicted to enable signaling receptor binding activity. Predicted to be involved in animal organ morphogenesis; neuron projection development; and tissue development. Predicted to be located in Golgi apparatus and extracellular region. Predicted to be active in basement membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08166891).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006181.3. 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
	NTN3	NM_006181.3	MANE Select	c.257G>A	p.Gly86Asp	missense	Exon 1 of 6	NP_006172.1	O00634

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN3	ENST00000293973.2	TSL:1 MANE Select	c.257G>A	p.Gly86Asp	missense	Exon 1 of 6	ENSP00000293973.1	O00634

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000106 AC: 22 AN: 207672 AF XY: 0.0000864

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000323

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000824

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000691 AC: 98 AN: 1418922 Hom.: 0 Cov.: 32 AF XY: 0.0000597 AC XY: 42 AN XY: 703312

African (AFR) AF: 0.00 AC: 0 AN: 32436

American (AMR) AF: 0.0000243 AC: 1 AN: 41218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24780

East Asian (EAS) AF: 0.00 AC: 0 AN: 39064

South Asian (SAS) AF: 0.00 AC: 0 AN: 82792

European-Finnish (FIN) AF: 0.000864 AC: 33 AN: 38188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 0.0000566 AC: 62 AN: 1096194

Other (OTH) AF: 0.0000340 AC: 2 AN: 58738

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

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

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000270 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000758 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.64	N
PhyloP100		0.40
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.065
Sift	Uncertain	0.024	D
Sift4G	Benign	0.067	T
Polyphen		0.085	B
Vest4		0.27
MVP		0.52
MPC		0.88
ClinPred		0.050	T
GERP RS		3.6
Varity_R		0.091
gMVP		0.47
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200322306; hg19: chr16-2521959;