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GeneBe

12-5494484-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001102654.2(NTF3):c.309C>T(p.Thr103=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,613,804 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0035 ( 10 hom. )

Consequence

NTF3
NM_001102654.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.49
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-5494484-C-T is Benign according to our data. Variant chr12-5494484-C-T is described in ClinVar as [Benign]. Clinvar id is 717685.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.49 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 374 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NTF3NM_001102654.2 linkuse as main transcriptc.309C>T p.Thr103= synonymous_variant 2/2 ENST00000423158.4
NTF3NM_002527.5 linkuse as main transcriptc.270C>T p.Thr90= synonymous_variant 1/1
NTF3XM_011520963.3 linkuse as main transcriptc.270C>T p.Thr90= synonymous_variant 2/2
NTF3XM_047428901.1 linkuse as main transcriptc.270C>T p.Thr90= synonymous_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NTF3ENST00000423158.4 linkuse as main transcriptc.309C>T p.Thr103= synonymous_variant 2/21 NM_001102654.2 P4P20783-2
NTF3ENST00000331010.7 linkuse as main transcriptc.270C>T p.Thr90= synonymous_variant 1/1 A1P20783-1
NTF3ENST00000543548.1 linkuse as main transcriptn.499C>T non_coding_transcript_exon_variant 2/23
NTF3ENST00000535299.5 linkuse as main transcriptn.232-12081C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00246
AC:
374
AN:
152130
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000700
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00663
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00415
Gnomad OTH
AF:
0.00288
GnomAD3 exomes
AF:
0.00205
AC:
514
AN:
250742
Hom.:
1
AF XY:
0.00204
AC XY:
277
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.000678
Gnomad AMR exome
AF:
0.000925
Gnomad ASJ exome
AF:
0.00566
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000471
Gnomad NFE exome
AF:
0.00345
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00353
AC:
5163
AN:
1461556
Hom.:
10
Cov.:
36
AF XY:
0.00342
AC XY:
2486
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.000827
Gnomad4 ASJ exome
AF:
0.00478
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000735
Gnomad4 NFE exome
AF:
0.00430
Gnomad4 OTH exome
AF:
0.00267
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00246
AC:
374
AN:
152248
Hom.:
1
Cov.:
32
AF XY:
0.00211
AC XY:
157
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.000698
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00663
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.00415
Gnomad4 OTH
AF:
0.00285
Alfa
AF:
0.00367
Hom.:
0
Bravo
AF:
0.00214
EpiCase
AF:
0.00311
EpiControl
AF:
0.00314

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeSep 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
0.12
Dann
Benign
0.71

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.

Other links and lift over

dbSNP: rs35988749; hg19: chr12-5603650; COSMIC: COSV58417356; API