Variant 12-5494440-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001102654.2(NTF3):c.265G>A(p.Gly89Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000427 in 1,613,118 control chromosomes in the GnomAD database, including 7 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 Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G89E) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 7 hom. )

Consequence

NTF3
NM_001102654.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.25

Variant links:

Genes affected

NTF3 (HGNC:8023): (neurotrophin 3) The protein encoded by this gene is a member of the neurotrophin family, that controls survival and differentiation of mammalian neurons. This protein is closely related to both nerve growth factor and brain-derived neurotrophic factor. It may be involved in the maintenance of the adult nervous system, and may affect development of neurons in the embryo when it is expressed in human placenta. NTF3-deficient mice generated by gene targeting display severe movement defects of the limbs. The mature peptide of this protein is identical in all mammals examined including human, pig, rat and mouse. [provided by RefSeq, Jul 2008]

NTF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040516257).

BS2

High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NTF3	NM_001102654.2 linkuse as main transcript	c.265G>A	p.Gly89Arg	missense_variant	2/2	ENST00000423158.4
NTF3	NM_002527.5 linkuse as main transcript	c.226G>A	p.Gly76Arg	missense_variant	1/1
NTF3	XM_011520963.3 linkuse as main transcript	c.226G>A	p.Gly76Arg	missense_variant	2/2
NTF3	XM_047428901.1 linkuse as main transcript	c.226G>A	p.Gly76Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTF3	ENST00000423158.4 linkuse as main transcript	c.265G>A	p.Gly89Arg	missense_variant	2/2	1	NM_001102654.2	P4	P20783-2
NTF3	ENST00000331010.7 linkuse as main transcript	c.226G>A	p.Gly76Arg	missense_variant	1/1			A1	P20783-1
NTF3	ENST00000543548.1 linkuse as main transcript	n.455G>A		non_coding_transcript_exon_variant	2/2	3
NTF3	ENST00000535299.5 linkuse as main transcript	n.232-12125G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000303

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00646

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000905

AC:

225

AN:

248686

Hom.:

AF XY:

0.00108

AC XY:

146

AN XY:

134842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00572

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000440

AC:

643

AN:

1460968

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

421

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00559

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000302

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00647

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000446

Hom.:

Bravo

AF:

0.000208

ExAC

AF:

0.000865

AC:

105

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hirschsprung disease, susceptibility to, 1

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Department of Genetics, Reproduction and Fetal Medicine., Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville.

Apr 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.29

.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.024

Sift

Benign

0.059

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.0050

.;B

Vest4

0.064

MutPred

0.23

.;Gain of methylation at G76 (P = 0.0231);

MVP

0.12

MPC

1.0

ClinPred

0.025

GERP RS

3.0

Varity_R

0.054

gMVP

0.13

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