15-88121445-C-A

Position:

• chr15-88121445-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+4826G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,072 control chromosomes in the GnomAD database, including 5,891 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 0.27 (5891 hom., cov: 33)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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]

NTRK3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1396+4826G>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.1396+4826G>T		intron_variant		1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40628 AN: 151954 Hom.: 5885 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.267 AC: 40665 AN: 152072 Hom.: 5891 Cov.: 33 AF XY: 0.260 AC XY: 19299 AN XY: 74322

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.245

Alfa AF: 0.230 Hom.: 2070

Bravo AF: 0.276

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2114252; hg19: chr15-88664676;