rs71578945

Positions:

• chr12-5432458-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -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/exons	MANE	Protein	UniProt
NTF3	NM_001102654.2	c.18+116C>G		intron_variant		ENST00000423158.4	NP_001096124.1
NTF3	XM_047428901.1	c.-22+1265C>G		intron_variant			XP_047284857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTF3	ENST00000423158.4	c.18+116C>G		intron_variant		1	NM_001102654.2	ENSP00000397297.2
NTF3	ENST00000535299.5	n.231+116C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00841 AC: 1276 AN: 151812 Hom.: 13 Cov.: 29

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.: 83 AF XY: 0.0113 AC XY: 5681 AN XY: 501436

Gnomad4 AFR exome AF: 0.00195

Gnomad4 AMR exome AF: 0.00406

Gnomad4 ASJ exome AF: 0.00143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00602

Gnomad4 FIN exome AF: 0.0228

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.00994

GnomAD4 genome AF: 0.00840 AC: 1276 AN: 151930 Hom.: 13 Cov.: 29 AF XY: 0.00848 AC XY: 630 AN XY: 74262

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00511

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00333

Gnomad4 FIN AF: 0.0236

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.0101 Hom.: 1

Bravo AF: 0.00718

Asia WGS AF: 0.00115 AC: 4 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	18
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71578945; hg19: chr12-5541624;