rs3784421

Positions:

• chr15-88090547-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012338.3(NTRK3):​c.1396+35724G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 152,214 control chromosomes in the GnomAD database, including 29 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 0.013 (29 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

Genes affected

NTRK3 (HGNC:8033): (neurotrophic receptor tyrosine kinase 3) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.1396+35724G>T		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.1396+35724G>T		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2048 AN: 152096 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.00581

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0134 AC: 2047 AN: 152214 Hom.: 29 Cov.: 32 AF XY: 0.0136 AC XY: 1015 AN XY: 74414

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00915

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.0908

Gnomad4 SAS AF: 0.00602

Gnomad4 FIN AF: 0.0177

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.0134 Hom.: 4

Bravo AF: 0.0123

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs3784421; hg19: chr15-88633778;