16-2471949-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006181.3(NTN3):​c.248C>T​(p.Ser83Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,559,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

NTN3
NM_006181.3 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.390
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2057944).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTN3NM_006181.3 linkc.248C>T p.Ser83Phe missense_variant Exon 1 of 6 ENST00000293973.2 NP_006172.1 O00634

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTN3ENST00000293973.2 linkc.248C>T p.Ser83Phe missense_variant Exon 1 of 6 1 NM_006181.3 ENSP00000293973.1 O00634

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000152
AC:
3
AN:
197004
Hom.:
0
AF XY:
0.00000909
AC XY:
1
AN XY:
110056
show subpopulations
Gnomad AFR exome
AF:
0.000160
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000398
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000568
AC:
8
AN:
1407308
Hom.:
0
Cov.:
32
AF XY:
0.00000431
AC XY:
3
AN XY:
696494
show subpopulations
Gnomad4 AFR exome
AF:
0.0000627
Gnomad4 AMR exome
AF:
0.0000757
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:
0.00000275
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152218
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000166
ExAC
AF:
0.00000846
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 23, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.248C>T (p.S83F) alteration is located in exon 1 (coding exon 1) of the NTN3 gene. This alteration results from a C to T substitution at nucleotide position 248, causing the serine (S) at amino acid position 83 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
18
DANN
Uncertain
0.97
DEOGEN2
Uncertain
0.52
D
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.62
T
M_CAP
Pathogenic
0.32
D
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.12
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.27
B
Vest4
0.21
MutPred
0.56
Loss of glycosylation at S83 (P = 6e-04);
MVP
0.47
MPC
0.47
ClinPred
0.13
T
GERP RS
-0.28
Varity_R
0.25
gMVP
0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs757946481; hg19: chr16-2521950; API