17-9022650-C-T

Variant summary

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

The NM_004822.3(NTN1):​c.277C>T​(p.Leu93Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,412,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NTN1
NM_004822.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92
Variant links:
Genes affected
NTN1 (HGNC:8029): (netrin 1) Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of netrin suggest that variation in netrin may be involved in cancer development. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTN1NM_004822.3 linkc.277C>T p.Leu93Phe missense_variant Exon 2 of 7 ENST00000173229.7 NP_004813.2 O95631
NTN1XM_006721595.4 linkc.277C>T p.Leu93Phe missense_variant Exon 2 of 7 XP_006721658.1 O95631
NTN1XM_047437096.1 linkc.277C>T p.Leu93Phe missense_variant Exon 2 of 7 XP_047293052.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTN1ENST00000173229.7 linkc.277C>T p.Leu93Phe missense_variant Exon 2 of 7 1 NM_004822.3 ENSP00000173229.2 O95631

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000212
AC:
3
AN:
1412240
Hom.:
0
Cov.:
31
AF XY:
0.00000286
AC XY:
2
AN XY:
698378
show subpopulations
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:
0.00000276
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.277C>T (p.L93F) alteration is located in exon 2 (coding exon 1) of the NTN1 gene. This alteration results from a C to T substitution at nucleotide position 277, causing the leucine (L) at amino acid position 93 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
0.098
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.56
D
Eigen
Benign
0.13
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.082
D
MetaRNN
Uncertain
0.48
T
MetaSVM
Benign
-0.39
T
MutationAssessor
Benign
0.41
N
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.26
Sift
Benign
0.27
T
Sift4G
Benign
0.27
T
Polyphen
0.62
P
Vest4
0.32
MutPred
0.50
Loss of catalytic residue at L93 (P = 0.1303);
MVP
0.78
ClinPred
0.85
D
GERP RS
4.8
Varity_R
0.43
gMVP
0.31

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: rs2091855536; hg19: chr17-8925967; API