Variant chr12-5494484-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

NTF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.49 with no splicing effect.

BS2

High AC in GnomAd4 at 374 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NTF3	NM_001102654.2 linkuse as main transcript	c.309C>T	p.Thr103=	synonymous_variant	2/2	ENST00000423158.4
NTF3	NM_002527.5 linkuse as main transcript	c.270C>T	p.Thr90=	synonymous_variant	1/1
NTF3	XM_011520963.3 linkuse as main transcript	c.270C>T	p.Thr90=	synonymous_variant	2/2
NTF3	XM_047428901.1 linkuse as main transcript	c.270C>T	p.Thr90=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTF3	ENST00000423158.4 linkuse as main transcript	c.309C>T	p.Thr103=	synonymous_variant	2/2	1	NM_001102654.2	P4	P20783-2
NTF3	ENST00000331010.7 linkuse as main transcript	c.270C>T	p.Thr90=	synonymous_variant	1/1			A1	P20783-1
NTF3	ENST00000543548.1 linkuse as main transcript	n.499C>T		non_coding_transcript_exon_variant	2/2	3
NTF3	ENST00000535299.5 linkuse as main transcript	n.232-12081C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

374

AN:

152130

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00246

AC:

374

AN:

152248

Hom.:

Cov.:

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.:

Bravo

AF:

0.00214

EpiCase

AF:

0.00311

EpiControl

AF:

0.00314

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 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.

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