dbSNP rs544995384: NTF3:p.Glu86Gly (chr12-5494432-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001102654.2(NTF3):c.257A>G(p.Glu86Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E86V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NTF3
NM_001102654.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009731829).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF3	NM_001102654.2 link	c.257A>G	p.Glu86Gly	missense_variant	Exon 2 of 2	ENST00000423158.4	NP_001096124.1	P20783-2
NTF3	NM_002527.5 link	c.218A>G	p.Glu73Gly	missense_variant	Exon 1 of 1		NP_002518.1	P20783-1
NTF3	XM_011520963.3 link	c.218A>G	p.Glu73Gly	missense_variant	Exon 2 of 2		XP_011519265.1	P20783-1
NTF3	XM_047428901.1 link	c.218A>G	p.Glu73Gly	missense_variant	Exon 2 of 2		XP_047284857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NTF3	ENST00000423158.4 link	c.257A>G	p.Glu86Gly	missense_variant	Exon 2 of 2	1	NM_001102654.2	ENSP00000397297.2	P20783-2
NTF3	ENST00000331010.7 link	c.218A>G	p.Glu73Gly	missense_variant	Exon 1 of 1	6		ENSP00000328738.6	P20783-1
NTF3	ENST00000543548.1 link	n.447A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
NTF3	ENST00000535299.5 link	n.232-12133A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

243416

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1458850

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725730

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111950

Other (OTH)

AF:

0.00

AC:

AN:

60294

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0097

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.23

.;N

PhyloP100

2.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.031

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.14

T;T

Polyphen

0.0

.;B

Vest4

0.077

MutPred

0.31

.;Gain of methylation at R74 (P = 0.0287);

MVP

0.15

MPC

0.99

ClinPred

0.16

GERP RS

0.81

PromoterAI

-0.034

Neutral

(source)

Varity_R

0.041

gMVP

0.24

Mutation Taster

=77/23

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over