Variant 12-95683710-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021229.4(NTN4):c.1182G>A(p.Pro394=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,599,610 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

NTN4
NM_021229.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00009276

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.46

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 12-95683710-C-T is Benign according to our data. Variant chr12-95683710-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643221.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.46 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NTN4	NM_021229.4 linkuse as main transcript	c.1182G>A	p.Pro394=	splice_region_variant, synonymous_variant	6/10	ENST00000343702.9	NP_067052.2
NTN4	NM_001329700.2 linkuse as main transcript	c.1182G>A	p.Pro394=	splice_region_variant, synonymous_variant	6/9		NP_001316629.1
NTN4	NM_001329701.2 linkuse as main transcript	c.1071G>A	p.Pro357=	splice_region_variant, synonymous_variant	6/10		NP_001316630.1
NTN4	NM_001329702.2 linkuse as main transcript	c.1071G>A	p.Pro357=	splice_region_variant, synonymous_variant	6/10		NP_001316631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN4	ENST00000343702.9 linkuse as main transcript	c.1182G>A	p.Pro394=	splice_region_variant, synonymous_variant	6/10	1	NM_021229.4	ENSP00000340998	P1	Q9HB63-1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

384

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00478

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00174

AC:

388

AN:

222774

Hom.:

AF XY:

0.00142

AC XY:

170

AN XY:

119838

show subpopulations

Gnomad AFR exome

AF:

0.00543

Gnomad AMR exome

AF:

0.00238

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.000121

Gnomad SAS exome

AF:

0.000143

Gnomad FIN exome

AF:

0.0000506

Gnomad NFE exome

AF:

0.000867

Gnomad OTH exome

AF:

0.00412

GnomAD4 exome

AF:

0.00105

AC:

1526

AN:

1447362

Hom.:

Cov.:

AF XY:

0.000971

AC XY:

698

AN XY:

718662

show subpopulations

Gnomad4 AFR exome

AF:

0.00607

Gnomad4 AMR exome

AF:

0.00263

Gnomad4 ASJ exome

AF:

0.0140

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000554

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.00253

AC:

385

AN:

152248

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00479

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00298

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

NTN4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000093

dbscSNV1_RF

Benign

0.0040

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