Variant chr16-2471922-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006181.3(NTN3):c.221G>C(p.Arg74Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000629 in 1,544,560 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 1 hom. )

Consequence

NTN3
NM_006181.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.862

Variant links:

Genes affected

NTN3 (HGNC:8030): (netrin 3) Predicted to enable signaling receptor binding activity. Predicted to be involved in animal organ morphogenesis; neuron projection development; and tissue development. Predicted to be located in Golgi apparatus and extracellular region. Predicted to be active in basement membrane. [provided by Alliance of Genome Resources, Apr 2022]

NTN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24563155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTN3	NM_006181.3 linkuse as main transcript	c.221G>C	p.Arg74Pro	missense_variant	1/6	ENST00000293973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTN3	ENST00000293973.2 linkuse as main transcript	c.221G>C	p.Arg74Pro	missense_variant	1/6	1	NM_006181.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00101

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000523

AC:

AN:

170048

Hom.:

AF XY:

0.000628

AC XY:

AN XY:

95564

show subpopulations

Gnomad AFR exome

AF:

0.0000964

Gnomad AMR exome

AF:

0.000411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000961

Gnomad OTH exome

AF:

0.000457

GnomAD4 exome

AF:

0.000643

AC:

895

AN:

1392264

Hom.:

Cov.:

AF XY:

0.000610

AC XY:

420

AN XY:

688606

show subpopulations

Gnomad4 AFR exome

AF:

0.0000320

Gnomad4 AMR exome

AF:

0.000398

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:

0.000787

Gnomad4 OTH exome

AF:

0.000434

GnomAD4 genome

AF:

0.000499

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.000521

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ExAC

AF:

0.000526

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2024

The c.221G>C (p.R74P) alteration is located in exon 1 (coding exon 1) of the NTN3 gene. This alteration results from a G to C substitution at nucleotide position 221, causing the arginine (R) at amino acid position 74 to be replaced by a proline (P). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

Eigen

Benign

0.044

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.25

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.56

Sift

Uncertain

0.021

Sift4G

Benign

0.070

Polyphen

0.97

Vest4

0.59

MVP

0.79

MPC

1.1

ClinPred

0.11

GERP RS

2.2

Varity_R

0.64

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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