rs10520676

Positions:

• chr15-88166407-G-A
• chr15-88166407-G-T

Variant summary

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

The NM_001012338.3(NTRK3):​c.395+17011C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,970 control chromosomes in the GnomAD database, including 5,775 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 0.26 (5775 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.395+17011C>T		intron_variant		ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.395+17011C>T		intron_variant		1	NM_001012338.3	ENSP00000485864

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39868 AN: 151852 Hom.: 5762 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.263 AC: 39922 AN: 151970 Hom.: 5775 Cov.: 32 AF XY: 0.261 AC XY: 19348 AN XY: 74254

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.258

Alfa AF: 0.218 Hom.: 5192

Bravo AF: 0.268

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.77

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: rs10520676; hg19: chr15-88709638;