17-9022593-C-T

Variant summary

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

The NM_004822.3(NTN1):​c.220C>T​(p.Pro74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

NTN1
NM_004822.3 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50
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.220C>T p.Pro74Ser missense_variant Exon 2 of 7 ENST00000173229.7 NP_004813.2 O95631
NTN1XM_006721595.4 linkc.220C>T p.Pro74Ser missense_variant Exon 2 of 7 XP_006721658.1 O95631
NTN1XM_047437096.1 linkc.220C>T p.Pro74Ser 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.220C>T p.Pro74Ser missense_variant Exon 2 of 7 1 NM_004822.3 ENSP00000173229.2 O95631

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
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:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.220C>T (p.P74S) 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 220, causing the proline (P) at amino acid position 74 to be replaced by a serine (S). 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
0.096
BayesDel_addAF
Uncertain
0.018
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.85
D
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.32
D
MetaRNN
Uncertain
0.69
D
MetaSVM
Uncertain
0.31
D
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-4.5
D
REVEL
Uncertain
0.64
Sift
Benign
0.081
T
Sift4G
Benign
0.088
T
Polyphen
0.93
P
Vest4
0.17
MutPred
0.80
Loss of catalytic residue at P73 (P = 0.0131);
MVP
0.78
ClinPred
0.98
D
GERP RS
3.6
Varity_R
0.51
gMVP
0.77

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: rs1051643472; hg19: chr17-8925910; API