Variant 12-5494901-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001102654.2(NTF3):c.726A>G(p.Ser242=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,614,208 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 7 hom. )

Consequence

NTF3
NM_001102654.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.165

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 12-5494901-A-G is Benign according to our data. Variant chr12-5494901-A-G is described in ClinVar as [Benign]. Clinvar id is 784229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.165 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00572 (871/152332) while in subpopulation AFR AF= 0.0185 (767/41562). AF 95% confidence interval is 0.0174. There are 8 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 871 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NTF3	NM_001102654.2 linkuse as main transcript	c.726A>G	p.Ser242=	synonymous_variant	2/2	ENST00000423158.4
NTF3	NM_002527.5 linkuse as main transcript	c.687A>G	p.Ser229=	synonymous_variant	1/1
NTF3	XM_011520963.3 linkuse as main transcript	c.687A>G	p.Ser229=	synonymous_variant	2/2
NTF3	XM_047428901.1 linkuse as main transcript	c.687A>G	p.Ser229=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTF3	ENST00000423158.4 linkuse as main transcript	c.726A>G	p.Ser242=	synonymous_variant	2/2	1	NM_001102654.2	P4	P20783-2
NTF3	ENST00000331010.7 linkuse as main transcript	c.687A>G	p.Ser229=	synonymous_variant	1/1			A1	P20783-1
NTF3	ENST00000535299.5 linkuse as main transcript	n.232-11664A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00572

AC:

870

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00189

AC:

475

AN:

251424

Hom.:

AF XY:

0.00153

AC XY:

208

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0184

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00744

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000869

AC:

1270

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000770

AC XY:

560

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00746

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000237

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00572

AC:

871

AN:

152332

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

404

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0185

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00329

Hom.:

Bravo

AF:

0.00617

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.000474

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	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.6

DANN

Benign

0.58

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

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