rs2009966

chr15-87997493-G-A

Variant summary

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

The NM_001012338.3(NTRK3):c.1585+35364C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,760 control chromosomes in the GnomAD database, including 17,768 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 0.47 (17768 hom., cov: 31)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.1585+35364C>T		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.1585+35364C>T		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70614 AN: 151642 Hom.: 17729 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.466 AC: 70700 AN: 151760 Hom.: 17768 Cov.: 31 AF XY: 0.459 AC XY: 34055 AN XY: 74164

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.441

Alfa AF: 0.430 Hom.: 7270

Bravo AF: 0.479

Asia WGS AF: 0.378 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.10
Dann	Benign	0.82

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: rs2009966; hg19: chr15-88540724;