Variant chr12-95710602-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000343702.9(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
ENST00000343702.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.18

Variant links:

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]

NTN4 links:

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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 GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTN4	NM_021229.4 linkuse as main transcript	c.1019C>A	p.Thr340Asn	missense_variant	5/10	ENST00000343702.9	NP_067052.2	Q9HB63-1
NTN4	NM_001329700.2 linkuse as main transcript	c.1019C>A	p.Thr340Asn	missense_variant	5/9		NP_001316629.1	Q9HB63-2B2RE43A8K3H6
NTN4	NM_001329701.2 linkuse as main transcript	c.908C>A	p.Thr303Asn	missense_variant	5/10		NP_001316630.1	Q9HB63-3A8K3H6
NTN4	NM_001329702.2 linkuse as main transcript	c.908C>A	p.Thr303Asn	missense_variant	5/10		NP_001316631.1	Q9HB63-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN4	ENST00000343702.9 linkuse as main transcript	c.1019C>A	p.Thr340Asn	missense_variant	5/10	1	NM_021229.4	ENSP00000340998.4		Q9HB63-1

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

474

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000757

AC:

190

AN:

251070

Hom.:

AF XY:

0.000509

AC XY:

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000317

AC:

463

AN:

1461746

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

177

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0105

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00311

AC:

474

AN:

152292

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000542

Hom.:

Bravo

AF:

0.00322

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.000289

AC:

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

Labcorp Genetics (formerly Invitae), Labcorp

May 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

T;.;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

T;.;T;T

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.6

L;.;.;L

MutationTaster

Benign

0.92

D;D;D;D

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.098

Sift

Benign

0.053

T;T;T;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.15

B;.;.;B

Vest4

0.20

MVP

0.61

MPC

0.39

ClinPred

0.0074

GERP RS

4.4

Varity_R

0.037

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over