chr12-5494621-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001102654.2(NTF3):​c.446G>A​(p.Arg149Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R149G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NTF3
NM_001102654.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2556602).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NTF3NM_001102654.2 linkuse as main transcriptc.446G>A p.Arg149Gln missense_variant 2/2 ENST00000423158.4
NTF3NM_002527.5 linkuse as main transcriptc.407G>A p.Arg136Gln missense_variant 1/1
NTF3XM_011520963.3 linkuse as main transcriptc.407G>A p.Arg136Gln missense_variant 2/2
NTF3XM_047428901.1 linkuse as main transcriptc.407G>A p.Arg136Gln missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NTF3ENST00000423158.4 linkuse as main transcriptc.446G>A p.Arg149Gln missense_variant 2/21 NM_001102654.2 P4P20783-2
NTF3ENST00000331010.7 linkuse as main transcriptc.407G>A p.Arg136Gln missense_variant 1/1 A1P20783-1
NTF3ENST00000535299.5 linkuse as main transcriptn.232-11944G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251372
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135880
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461870
Hom.:
0
Cov.:
36
AF XY:
0.00000275
AC XY:
2
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000659
Hom.:
0

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 submitterclinical testingAmbry GeneticsJul 20, 2021The c.407G>A (p.R136Q) alteration is located in exon 1 (coding exon 1) of the NTF3 gene. This alteration results from a G to A substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a glutamine (Q). 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
Benign
0.072
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
.;T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.80
.;N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.36
N;N
REVEL
Benign
0.055
Sift
Benign
0.18
T;T
Sift4G
Benign
0.66
T;T
Polyphen
0.31
.;B
Vest4
0.096
MutPred
0.33
.;Loss of MoRF binding (P = 0.0591);
MVP
0.34
MPC
2.0
ClinPred
0.81
D
GERP RS
5.5
Varity_R
0.12
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1252054668; hg19: chr12-5603787; COSMIC: COSV100451084; COSMIC: COSV100451084; API