Genetic Variant NTF3:c.18+116C>G (chr12-5432458-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001102654.2(NTF3):c.18+116C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,142,298 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0084 ( 13 hom., cov: 29)

Exomes 𝑓: 0.011 ( 83 hom. )

Consequence

NTF3
NM_001102654.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

2 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BS2

High AC in GnomAd4 at 1276 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF3	NM_001102654.2 link	c.18+116C>G		intron_variant	Intron 1 of 1	ENST00000423158.4	NP_001096124.1	P20783-2
NTF3	XM_047428901.1 link	c.-22+1265C>G		intron_variant	Intron 1 of 1		XP_047284857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF3	ENST00000423158.4 link	c.18+116C>G		intron_variant	Intron 1 of 1	1	NM_001102654.2	ENSP00000397297.2		P20783-2
NTF3	ENST00000535299.5 link	n.231+116C>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.00841

AC:

1276

AN:

151812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00505

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00333

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00336

GnomAD4 exome

AF:

0.0114

AC:

11246

AN:

990368

Hom.:

AF XY:

0.0113

AC XY:

5681

AN XY:

501436

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

24646

American (AMR)

AF:

0.00406

AC:

148

AN:

36466

Ashkenazi Jewish (ASJ)

AF:

0.00143

AC:

AN:

20320

East Asian (EAS)

AF:

0.00

AC:

AN:

36156

South Asian (SAS)

AF:

0.00602

AC:

413

AN:

68580

European-Finnish (FIN)

AF:

0.0228

AC:

797

AN:

34904

Middle Eastern (MID)

AF:

0.00701

AC:

AN:

3564

European-Non Finnish (NFE)

AF:

0.0130

AC:

9343

AN:

721162

Other (OTH)

AF:

0.00994

AC:

443

AN:

44570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

567

1135

1702

2270

2837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00840

AC:

1276

AN:

151930

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

630

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.00229

AC:

AN:

41440

American (AMR)

AF:

0.00511

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00333

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.0236

AC:

250

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0122

AC:

827

AN:

67960

Other (OTH)

AF:

0.00332

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00718

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.1

PromoterAI

-0.10

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over