chr12-95710602-G-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_021229.4(NTN4):c.1019C>A(p.Thr340Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000581 in 1,614,038 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 1 hom. )
Consequence
NTN4
NM_021229.4 missense
NM_021229.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 2.18
Genes affected
NTN4 (HGNC:13658): (netrin 4) This gene encodes a member of the netrin family of proteins, which function in various biological processes including axon guidance, tumorogenesis, and angiogenesis. Netrins are laminin-related proteins that have an N-terminal laminin-type domain, epidermal growth factor-like repeat domain, and a positively charged heparin-binding domain at the C-terminus. The protein encoded by this gene is involved in processes including neurite growth and migration, angiogenesis and mural cell adhesion to endothelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.018047392).
BP6
?
Variant 12-95710602-G-T is Benign according to our data. Variant chr12-95710602-G-T is described in ClinVar as [Benign]. Clinvar id is 734013.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NTN4 | NM_021229.4 | c.1019C>A | p.Thr340Asn | missense_variant | 5/10 | ENST00000343702.9 | |
NTN4 | NM_001329700.2 | c.1019C>A | p.Thr340Asn | missense_variant | 5/9 | ||
NTN4 | NM_001329701.2 | c.908C>A | p.Thr303Asn | missense_variant | 5/10 | ||
NTN4 | NM_001329702.2 | c.908C>A | p.Thr303Asn | missense_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NTN4 | ENST00000343702.9 | c.1019C>A | p.Thr340Asn | missense_variant | 5/10 | 1 | NM_021229.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00311 AC: 474AN: 152174Hom.: 2 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
474
AN:
152174
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000757 AC: 190AN: 251070Hom.: 0 AF XY: 0.000509 AC XY: 69AN XY: 135664
GnomAD3 exomes
AF:
AC:
190
AN:
251070
Hom.:
AF XY:
AC XY:
69
AN XY:
135664
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000317 AC: 463AN: 1461746Hom.: 1 Cov.: 31 AF XY: 0.000243 AC XY: 177AN XY: 727158
GnomAD4 exome
AF:
AC:
463
AN:
1461746
Hom.:
Cov.:
31
AF XY:
AC XY:
177
AN XY:
727158
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00311 AC: 474AN: 152292Hom.: 2 Cov.: 32 AF XY: 0.00278 AC XY: 207AN XY: 74460
GnomAD4 genome
?
AF:
AC:
474
AN:
152292
Hom.:
Cov.:
32
AF XY:
AC XY:
207
AN XY:
74460
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
47
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
121
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 09, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;D
Sift4G
Benign
T;T;T;T
Polyphen
B;.;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at