chr12-5494441-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001102654.2(NTF3):c.266G>A(p.Gly89Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,612,718 control chromosomes in the GnomAD database, including 4,527 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G89R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.080 ( 1149 hom., cov: 31)

Exomes 𝑓: 0.022 ( 3378 hom. )

Consequence

NTF3
NM_001102654.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.88

Publications

17 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003197819).

BP6

Variant 12-5494441-G-A is Benign according to our data. Variant chr12-5494441-G-A is described in ClinVar as Benign. ClinVar VariationId is 599416.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102654.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTF3	NM_001102654.2	MANE Select	c.266G>A	p.Gly89Glu	missense	Exon 2 of 2	NP_001096124.1	P20783-2
	NTF3	NM_002527.5		c.227G>A	p.Gly76Glu	missense	Exon 1 of 1	NP_002518.1	P20783-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NTF3	ENST00000423158.4	TSL:1 MANE Select	c.266G>A	p.Gly89Glu	missense	Exon 2 of 2	ENSP00000397297.2	P20783-2
NTF3	ENST00000331010.7	TSL:6	c.227G>A	p.Gly76Glu	missense	Exon 1 of 1	ENSP00000328738.6	P20783-1
NTF3	ENST00000543548.1	TSL:3	n.456G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0796

AC:

12087

AN:

151776

Hom.:

1139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.00755

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00225

Gnomad OTH

AF:

0.0668

GnomAD2 exomes

AF:

0.0689

AC:

17118

AN:

248484

AF XY:

0.0539

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.00875

Gnomad NFE exome

AF:

0.00206

Gnomad OTH exome

AF:

0.0430

GnomAD4 exome

AF:

0.0218

AC:

31810

AN:

1460824

Hom.:

3378

Cov.:

AF XY:

0.0198

AC XY:

14385

AN XY:

726784

show subpopulations

African (AFR)

AF:

0.201

AC:

6746

AN:

33480

American (AMR)

AF:

0.271

AC:

12126

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00283

AC:

AN:

26136

East Asian (EAS)

AF:

0.175

AC:

6947

AN:

39700

South Asian (SAS)

AF:

0.0251

AC:

2169

AN:

86258

European-Finnish (FIN)

AF:

0.00801

AC:

420

AN:

52414

Middle Eastern (MID)

AF:

0.0121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00115

AC:

1279

AN:

1111978

Other (OTH)

AF:

0.0328

AC:

1979

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1792

3584

5376

7168

8960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

488

976

1464

1952

2440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0799

AC:

12135

AN:

151894

Hom.:

1149

Cov.:

AF XY:

0.0819

AC XY:

6078

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.193

AC:

7987

AN:

41390

American (AMR)

AF:

0.183

AC:

2786

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.159

AC:

812

AN:

5108

South Asian (SAS)

AF:

0.0341

AC:

163

AN:

4784

European-Finnish (FIN)

AF:

0.00755

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00227

AC:

154

AN:

67980

Other (OTH)

AF:

0.0680

AC:

143

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

501

1002

1502

2003

2504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0305

Hom.:

1108

Bravo

AF:

0.102

ESP6500AA

AF:

0.186

AC:

819

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.0613

AC:

7437

Asia WGS

AF:

0.107

AC:

371

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00142

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aganglionic megacolon (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.7

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.26

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

0.61

REVEL

Benign

0.065

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.018

MPC

1.1

ClinPred

0.0014

GERP RS

4.8

PromoterAI

0.011

Neutral

(source)

Varity_R

0.029

gMVP

0.084

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over